Advancements in Polymer-Assisted Layer-by-Layer Fabrication of Wearable Sensors for Health Monitoring.

Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.

High-efficiency and economical uranium extraction from seawater with easily prepared supramolecular complexes.

Developing effective adsorbents for uranium extraction from natural seawater is strategically significant for the sustainable fuel supply of nuclear energy. Herein, stable and low-cost supramolecular complexes (PA-bPEI complexes) were facilely constructed through the assembly of phytic acid and hyperbranched polyethyleneimine based on the multiple modes of electrostatic interaction and hydrogen bonding. The PA-bPEI complexes exhibited not only high uptake (841.7 mg g-1) and selectivity (uranium/vanadium selectivity = 84.1) toward uranium but also good antibacterial ability against biofouling. Mechanism analysis revealed that phosphate chelating groups and amine assistant groups coordinated the uranyl ions together with a high affinity. To be more suitable for practical applications, powdery PA-bPEI complexes were compounded with sodium alginate to fabricate various macroscopic adsorbents with engineered forms, which achieved an extraction capacity of 9.0 mg g-1 in natural seawater after 50 days of testing. Impressively, the estimated economic cost of the macroscopic adsorbent for uranium extraction from seawater ($96.5 âˆ¼ 138.1 kg-1 uranium) was lower than that of all currently available uranium adsorbents. Due to their good uranium extraction performance and low economic cost, supramolecular complex-based adsorbents show great potential for industrial uranium extraction from seawater.

Limits of economy and fidelity for programmable assembly of size-controlled triply periodic polyhedra.

We propose and investigate an extension of the Caspar-Klug symmetry principles for viral capsid assembly to the programmable assembly of size-controlled triply periodic polyhedra, discrete variants of the Primitive, Diamond, and Gyroid cubic minimal surfaces. Inspired by a recent class of programmable DNA origami colloids, we demonstrate that the economy of design in these crystalline assemblies-in terms of the growth of the number of distinct particle species required with the increased size-scale (e.g., periodicity)-is comparable to viral shells. We further test the role of geometric specificity in these assemblies via dynamical assembly simulations, which show that conditions for simultaneously efficient and high-fidelity assembly require an intermediate degree of flexibility of local angles and lengths in programmed assembly. Off-target misassembly occurs via incorporation of a variant of disclination defects, generalized to the case of hyperbolic crystals. The possibility of these topological defects is a direct consequence of the very same symmetry principles that underlie the economical design, exposing a basic tradeoff between design economy and fidelity of programmable, size controlled assembly.

Surface-Patterned DNA Origami Rulers Reveal Nanoscale Distance Dependency of the Epidermal Growth Factor Receptor Activation.

The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate "Multiscale Origami Structures As Interface for Cells" (MOSAIC), to enable the systematic investigation of the effect of the nanoscale spacing of epidermal growth factor (EGF) ligands on the activation of the EGF receptor (EGFR). MOSAIC-based analyses revealed that EGF distances of about 30-40 nm led to the highest response in EGFR activation of adherent MCF7 and Hela cells. Our study emphasizes the significance of DNA-based platforms for the detailed investigation of the molecular mechanisms of cellular signaling cascades.

Strain Sensors Made of MXene, CNTs, and TPU/PSF Asymmetric Structure Films with Large Tensile Recovery and Applied in Human Health Monitoring.

Designing flexible wearable sensors with a wide sensing range, high sensitivity, and high stability is a vulnerable research direction with a futuristic field to study. In this paper, Ti3C2Tx MXene/carbon nanotube (CNT)/thermoplastic polyurethane (TPU)/polysulfone (PSF) composite films with excellent sensor performance were obtained by self-assembly of conductive fillers in TPU/PSF porous films with an asymmetric structure through vacuum filtration, and the porous films were prepared by the phase inversion method. The composite films consist of the upper part with finger-like "cavities" filled by MXene/CNTs, which reduces the microcracks in the conductive network during the tensile process, and the lower part has smaller apertures of a relatively dense resin cortex assisting the recovery process. The exclusive layer structure of the MXene/CNTs/TPU/PSF film sensor, with a thickness of 46.95 µm, contains 0.0339 mg/cm2 single-walled carbon nanotubes (SWNTs) and 0.348 mg/cm2 MXene only, providing functional range (0-80.7%), high sensitivity (up to 1265.18), and excellent stability and durability (stable sensing under 2300 fatigue tests, viable to the initial resistance), endurably cycled under large strains with serious damage to the conductive network. Finally, the MXene/CNTs/TPU/PSF film sensor is usable for monitoring pulse, swallow, tiptoe, and various joint bends in real time and distributing effective electrical signals. This paper implies that the MXene/CNTs/TPU/PSF film sensor has broad prospects in pragmatic applications.

The Spicy Science of Dendrimers in the Realm of Cancer Nanomedicine: A Report from the COST Action CA17140 Nano2Clinic.

COST Action CA17140 Cancer Nanomedicine-from the bench to the bedside (Nano2Clinic,) is the first, pan-European interdisciplinary network of representatives from academic institutions and small and medium enterprises including clinical research organizations (CROs) devoted to the development of nanosystems carrying anticancer drugs from their initial design, preclinical testing of efficacy, pharmacokinetics and toxicity to the preparation of detailed protocols needed for the first phase of their clinical studies. By promoting scientific exchanges, technological implementation, and innovative solutions, the action aims at providing a timely instrument to rationalize and focus research efforts at the European level in dealing with the grand challenge of nanomedicine translation in cancer, one of the major and societal-burdening human pathologies. Within CA17140, dendrimers in all their forms (from covalent to self-assembling dendrons) play a vital role as powerful nanotheranostic agents in oncology; therefore, the purpose of this review work is to gather and summarize the major results in the field stemming from collaborative efforts in the framework of the European Nano2Clinic COST Action.

Self-Healing, Reconfigurable, Thermal-Switching, Transformative Electronics for Health Monitoring.

Soft, deformable electronic devices provide the means to monitor physiological information and health conditions for disease diagnostics. However, their practical utility is limited due to the lack of intrinsical thermal switching for mechanically transformative adaptability and self-healing capability against mechanical damages. Here, the design concepts, materials and physics, manufacturing approaches, and application opportunities of self-healing, reconfigurable, thermal-switching device platforms based on hyperbranched polymers and biphasic liquid metal are reported. The former provides excellent self-healing performance and unique tunable stiffness and adhesion regulated by temperature for the on-skin switch, whereas the latter results in liquid metal circuits with extreme stretchability (>900%) and high conductivity (3.40 × 104  S cm-1 ), as well as simple recycling capability. Triggered by the increased temperature from the skin surface, a multifunctional device platform can conveniently conform and strongly adhere to the hierarchically textured skin surface for non-invasive, continuous, comfortable health monitoring. Additionally, the self-healing and adhesive characteristics allow multiple multifunctional circuit components to assemble and completely wrap on 3D curvilinear surfaces. Together, the design, manufacturing, and proof-of-concept demonstration of the self-healing, transformative, and self-assembled electronics open up new opportunities for robust soft deformable devices, smart robotics, prosthetics, and Internet-of-Things, and human-machine interfaces on irregular surfaces.

Simulations of DNA-Origami Self-Assembly Reveal Design-Dependent Nucleation Barriers.

Nucleation is the rate-determining step in the kinetics of many self-assembly processes. However, the importance of nucleation in the kinetics of DNA-origami self-assembly, which involves both the binding of staple strands and the folding of the scaffold strand, is unclear. Here, using Monte Carlo simulations of a lattice model of DNA origami, we find that some, but not all, designs can have a nucleation barrier and that this barrier disappears at lower temperatures, rationalizing the success of isothermal assembly. We show that the height of the nucleation barrier depends primarily on the coaxial stacking of staples that are adjacent on the same helix, a parameter that can be modified with staple design. Creating a nucleation barrier to DNA-origami assembly could be useful in optimizing assembly times and yields, while eliminating the barrier may allow for fast molecular sensors that can assemble/disassemble without hysteresis in response to changes in the environment.

Assessment of Cell-Material Interactions in Three Dimensions through Dispersed Coaggregation of Microsized Biomaterials into Tissue Spheroids.

In biomaterials R&D, conventional monolayer cell culture on flat/planar material samples, such as films, is still commonly employed at early stages of the assessment of interactions of cells with candidate materials considered for a biomedical application. In this feasibility study, an approach for the assessment of 3D cell-material interactions through dispersed coaggregation of microparticles from biomaterials into tissue spheroids is presented. Biomaterial microparticles can be created comparatively quickly and easily, allow the miniaturization of the assessment platform, and enable an unhindered remodeling of the dynamic cell-biomaterial system at any time. The aggregation of the microsized biomaterials and the cells is supported by low-attachment round-bottom microwells from thin polymer films arranged in densely packed arrays. The study is conducted by the example of MG63 osteoblast-like and human mesenchymal stem/stromal cells, and a small library of model microbiomaterials related to bone repair and regeneration. For the proof of concept, example interactions including cell adhesion to the material, the hybrid spheroids' morphology, size, and shape, material-associated cell death, cell metabolic activity, cell proliferation, and (osteogenic) differentiation are investigated. The cells in the spheroids are shown to respond to differences in the microbiomaterials' properties, their amounts, and the duration of interaction with them.

Cell-in-Catalytic-Shell Nanoarchitectonics: Catalytic Empowerment of Individual Living Cells by Single-Cell Nanoencapsulation.

Cell-in-shell biohybrid structures, synthesized by encapsulating individual living cells with exogenous materials, have emerged as exciting functional entities for engineered living materials, with emergent properties outside the scope of biochemical modifications. Artificial exoskeletons have, to date, provided physicochemical shelters to the cells inside in the first stage of technological development, and further advances in the field demand catalytically empowered, cellular hybrid systems that augment the biological functions of cells and even introduce completely new functions to the cells. This work describes a facile and generalizable strategy for empowering living cells with extrinsic catalytic capability through nanoencapsulation of living cells with a supramolecular metal-organic complex of Fe3+ and benzene-1,3,5-tricarboxylic acid (BTC). A series of enzymes are embedded in situ, without loss of catalytic activity, in the Fe3+ -BTC shells, not to mention the superior characteristics of cytocompatible and rapid shell-forming processes. The nanoshell enhances the catalytic efficiency of multienzymatic cascade reactions by confining reaction intermediates to its internal voids and the nanoencapsulated cells acquire exogenous biochemical functions, including enzymatic cleavage of lethal octyl-ß-d-glucopyranoside into d-glucose, with autonomous cytoprotection. The system will provide a versatile, nanoarchitectonic tool for interfacing biological cells with functional materials, especially for catalytic bioempowerment of living cells.

Self-Assembly of All-DNA Rods with Controlled Patchiness.

Double-stranded DNA (dsDNA) fragments exhibit noncovalent attractive interactions between their tips. It is still unclear how DNA liquid crystal self-assembly is affected by such blunt-end attractions. It is demonstrated that stiff dsDNA fragments with moderate aspect ratio can specifically self-assemble in concentrated aqueous solutions into different types of smectic mesophases on the basis of selectively screening of blunt-end DNA stacking interactions. To this end, this type of attractions are engineered at the molecular level by constructing DNA duplexes where the attractions between one or both ends are screened by short hairpin caps. All-DNA bilayer and monolayer smectic-A type of phases, as well as a columnar phase, can be stabilized by controlling attractions strength. The results imply that the so far elusive smectic-A in DNA rod-like liquid crystals is a thermodynamically stable phase. The existence of the bilayer smectic phase is confirmed by Monte-Carlo simulations of hard cylinders decorated with one attractive terminal site. This work demonstrates that DNA blunt-ends behave as well-defined monovalent attractive patches whose strength and position can be potentially precisely tuned, highlighting unique opportunities concerning the stabilization of nonconventional DNA-based lyotropic liquid crystal phases assembled by all-DNA patchy particles with arbitrary geometry and composition.

Quantitative Assessment of Chirality of Protein Secondary Structures and Phenylalanine Peptide Nanotubes.

In this study we consider the features of spatial-structure formation in proteins and their application in bioengineering. Methods for the quantitative assessment of the chirality of regular helical and irregular structures of proteins are presented. The features of self-assembly of phenylalanine (F) into peptide nanotubes (PNT), which form helices of different chirality, are also analyzed. A method is proposed for calculating the magnitude and sign of the chirality of helix-like peptide nanotubes using a sequence of vectors for the dipole moments of individual peptides.

In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model.

In vitro prevascularization has the potential to address the challenge of maintaining cell viability at the core of engineered constructs, such as bone substitutes, and to improve the survival of tissue grafts by allowing quicker anastomosis to the host microvasculature. The self-assembly approach of tissue engineering allows the production of biomimetic bone-like tissue constructs including extracellular matrix and living human adipose-derived stromal/stem cells (hASCs) induced towards osteogenic differentiation. We hypothesized that the addition of endothelial cells could improve osteogenesis and biomineralization during the production of self-assembled human bone-like tissues using hASCs. Additionally, we postulated that these prevascularized constructs would consequently improve graft survival and bone repair of rat calvarial bone defects. This study shows that a dense capillary network spontaneously formed in vitro during tissue biofabrication after two weeks of maturation. Despite reductions in osteocalcin levels and hydroxyapatite formation in vitro in prevascularized bone-like tissues (35 days of culture), in vivo imaging of prevascularized constructs showed an improvement in cell survival without impeding bone healing after 12 weeks of implantation in a calvarial bone defect model (immunocompromised male rats), compared to their stromal counterparts. Globally, these findings establish our ability to engineer prevascularized bone-like tissues with improved functional properties.

Tabletized Supramolecular Assemblies for Sublingual Peptide Immunization.

Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the costly requirements for cold-chain distribution and trained medical personnel to administer the vaccines. A heat-stable and highly porous tablet vaccine that can be administered sublingually via simple dissolution under the tongue is described. SIMPL tablet vaccines (Supramolecular IMmunization with Peptides subLingually) are produced by freeze-drying a mixture of self-assembling peptide-polymer nanofibers, sugars, and adjuvant. Sublingual immunization with SIMPL tablets raises antibody responses against both a model epitope from ovalbumin and a clinically relevant epitope from Mycobacterium tuberculosis. Further, sublingual antibody responses are not diminished after heating the tablets for 1 week at 45 °C, in contrast to a more conventional carrier vaccine (KLH). This approach directly addresses the need for a heat-stable and easily deliverable vaccine to improve equity in global vaccine coverage.

Well-Based Antibody Arrays.

Multiplex immunoassays are important tools in basic research and diagnostics. The ability to accurately quantify the presence of several antigens within an individual sample all at once has been useful in developing a proteomics view of biology. This in turn has enabled the development of disease-associated immunodiagnostic panels for better prognosis and well-being. Moreover, it is well understood that such multiplexing approaches lend themselves to automation, thereby reducing labor while providing the ability to dramatically conserve both reagent and sample all of which will reduce the cost per test. Here we describe various methods to create and use multiplex immunoassays in the wells of microtiter plates or similar formats.

Quantitative assessment of morphological traits of planktonic bacterial aggregates.

The efficiency of multi-strain planktonic flocs of bacteria as biocatalytic agents in aqueous media depends to a considerable extent on their three-dimensional aggregation patterns. Yet, numerical methodologies for full characterization of such heterogeneous biomass structures are largely missing. In this work we present a descriptive methodology for quantitatively portraying and identifying suspended cell clumps formed by planktonic bacteria. In order to benchmark the procedure, we tackled the behavior of cells of the environmental and biotechnologically robust species Pseudomonas putida whose surfaces were decorated with genetically encoded adhesins. Upon induction, such adhesins promoted specific inter-bacterial attachment leading to controllable and tractable floc formation in suspension. Microscopy and flow cytometry data were then gathered and further analyzed by means of a distinct metric set. Applying these parameters permitted creating comparable clumping footprints for every sample at both single-cell and population level. The hereby described approach provides a rigorous frame for following the assembly and organization of complex microbial communities as planktonic flocs.

Excogitation and Assessment of Curcumin-Vitamin E Self-assembly PEGylated Nanoparticles by the Route of Oral Administration.

Curcumin (CUR) has attracted wide research interests due to its abundant bioactivities and potential advantages in cancer treatment. But the poor water solubility, instability, and quick metabolization and elimination after oral administration severely restrict the efficacy and further clinical application of CUR. Derivation is an approach often used to improve the druggability of active ingredients, so the study aim to prepare a CUR derivate with better stability, satisfactory pharmacokinetics, and inherent self-assembled ability in contrast with CUR. The derivate was designed and evaluated in vitro and in vivo. Vitamin E (VE) was used to perform the esterification reaction with CUR, and the cytotoxicity of derivative CUR-VE ester on MCF-7 tumor cells was similar to CUR. Besides the better stability in simulated gastric and intestinal fluid, plasma and liver homogenate, the self-assembly CUR-VE nanoparticles were fabricated by feasible and controllable nanoprecipitation method. The Transmission Electron Microscope (TEM) showed CUR-VE NPs were spherical with an average particle size of 172.9 nm, and drug loading was up to 93%. CUR-VE NPs exhibited a sustained-release behavior and fitted to Fick's diffusion mechanism. Differential Scanning Calorimeter (DSC), X-ray Powder Diffractometer (XRPD) and Fourier Transform Infrared Spectrometer (FTIR) declared no crystalline substances were formed, and the self-assembly process of CUR-VE relied on driving forces including van der Waals forces, hydrogen bonding forces, intermolecular forces. In pharmacokinetics, Cmax and AUC0-∞ of CUR-VE NPs by the route of oral administration were (104.69 ± 40.72) ng/mL and (3496.92 ± 1088.93) ng/mL∗h, which were about three times and 18 times more compared with CUR. The eliminated half-time of CUR-VE extended to 28 h ascribed to the outstanding stability and surface PEGylation of NPs. It prompted that appropriately PEGylated NPs via oral administration was beneficial to prolong systemic circulation similar to intravenous PEGylated NPs. In summary, the study provides a convenient way to fabricate the self-assembled CUR-VE NPs qualified with high drug loading, satisfactory stability and desired pharmacokinetics. CUR-VE has the potent advantage to be an ideal substitute for CUR in the future of healthcare and clinical application.

Lignin for Bioeconomy: The Present and Future Role of Technical Lignin.

Lignin, the term commonly used in literature, represents a group of heterogeneous aromatic compounds of plant origin. Protolignin or lignin in the cell wall is entirely different from the commercially available technical lignin due to changes during the delignification process. In this paper, we assess the status of lignin valorization in terms of commercial products. We start with existing knowledge of the lignin/protolignin structure in its native form and move to the technical lignin from various sources. Special attention is given to the patents and lignin-based commercial products. We observed that the technical lignin-based commercial products utilize coarse properties of the technical lignin in marketed formulations. Additionally, the general principles of polymers chemistry and self-assembly are difficult to apply in lignin-based nanotechnology, and lignin-centric investigations must be carried out. The alternate upcoming approach is to develop lignin-centric or lignin first bio-refineries for high-value applications; however, that brings its own technological challenges. The assessment of the gap between lab-scale applications and lignin-based commercial products delineates the challenges lignin nanoparticles-based technologies must meet to be a commercially viable alternative.

Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies.

Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.

How a Virus Circumvents Energy Barriers to Form Symmetric Shells.

Previous self-assembly experiments on a model icosahedral plant virus have shown that, under physiological conditions, capsid proteins initially bind to the genome through an en masse mechanism and form nucleoprotein complexes in a disordered state, which raises the question as to how virions are assembled into a highly ordered structure in the host cell. Using small-angle X-ray scattering, we find out that a disorder-order transition occurs under physiological conditions upon an increase in capsid protein concentrations. Our cryo-transmission electron microscopy reveals closed spherical shells containing in vitro transcribed viral RNA even at pH 7.5, in marked contrast with the previous observations. We use Monte Carlo simulations to explain this disorder-order transition and find that, as the shell grows, the structures of disordered intermediates in which the distribution of pentamers does not belong to the icosahedral subgroups become energetically so unfavorable that the caps can easily dissociate and reassemble, overcoming the energy barriers for the formation of perfect icosahedral shells. In addition, we monitor the growth of capsids under the condition that the nucleation and growth is the dominant pathway and show that the key for the disorder-order transition in both en masse and nucleation and growth pathways lies in the strength of elastic energy compared to the other forces in the system including protein-protein interactions and the chemical potential of free subunits. Our findings explain, at least in part, why perfect virions with icosahedral order form under different conditions including physiological ones.