Highly Stretchable, Self-Healing, and Sensitive E-Skins at -78 °C for Polar Exploration.

Ultralow temperature-tolerant electronic skins (e-skins) can endow polar robots with tactile feedback for exploring in extremely cold polar environments. However, it remains a challenge to develop e-skins that enable sensitive touch sensation and self-healing at ultralow temperatures. Herein, we describe the development of a sensitive robotic hand e-skin that can stretch, self-heal, and sense at temperatures as low as -78 °C. The elastomeric substrate of this e-skin is based on poly(dimethylsiloxane) supramolecular polymers and multistrength dynamic H-bonds, in particular with quadruple H-bonding motifs (UPy). The structure-performance relationship of the elastomer at ultralow temperatures is investigated. The results show that elastomers with side-chain UPy units exhibit higher stretchability (∼3257%) and self-healing efficiency compared to those with main-chain UPy units. This is attributed to the lower binding energy variation and lower potential well. Based on the elastomer with side-chain UPy and man-made electric ink, a sensitive robotic hand e-skin for usage at -78 °C is constructed to precisely sense the shape of objects and specific symbols, and its sensation can completely self-recover after being damaged. The findings of this study contribute to the concept of using robotic hands with e-skins in polar environments that make human involvement limited, dangerous, or impossible.

2D nanomaterial-based 3D network hydrogels for anti-infection therapy.

Two-dimensional nanomaterials (2D NMs) refer to nanomaterials that possess a planar topography with a thickness of one or several atomic layers. Due to their large specific surface areas, atomic thickness, rough edges, and electron confinement in two dimensions, they have emerged as promising antimicrobial agents over antibiotics in combating bacterial infections. However, 2D NMs encounter issues such as low bio-safety, easy aggregation, and limited tissue penetration efficiency. To address these concerns, hydrogels with three-dimensional (3D) networks have been developed to encapsulate 2D NMs, aiming to enhance their biocompatibility, biodegradability, and ability to regulate and remodel the tissue microenvironment at the infected site. This review systematically summarizes the current studies on 2D NM-based antibacterial hydrogels with 3D network structures (named 2N3Hs). Firstly, we introduce the emerging types of 2N3Hs and describe their antibacterial actions. Subsequently, we discuss the applications of 2N3Hs in three biomedical fields, including wound dressing, cancer treatment, and bone regeneration. Finally, we conclude the review with current challenges and future developments for 2N3Hs, highlighting their potential as a promising choice for next-generation biomedical devices, particularly in the field of tissue engineering and regenerative medicine. This review aims to provide a comprehensive and panoramic overview of anti-infective 2N3Hs for various biomedical applications.

Reusable Zwitterionic Porous Organic Polymers for Bilirubin Removal in Serum.

Herein, we report a straightforward strategy to construct reusable, hemocompatible, and highly efficient bilirubin adsorbents by installing zwitterionic modules into a porous organic polymer (POP) for hemoperfusion application. Three types of zwitterions with different amounts are used to evaluate their impacts on the characteristics of POPs, including carboxybetaine methacrylate (CB), sulfobetaine methacrylate (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Results show that zwitterions can improve hemocompatibility, hydrophilicity, and bilirubin uptake of the POP. Among all zwitterionic POPs, POP-CB-40% exhibits the best bilirubin uptake, ∼46.5 times enhancement compared with the non-zwitterionic POP in 100% serum. This enhancement can be attributed to the improved hydrophilicity and protein resistance ability in biological solutions. More importantly, the reusability test shows that POP-CB-40% maintains ∼99% of bilirubin uptake capacity at fifth recycling in 100% serum. Findings in this work provide a guideline for the design of biocompatible and efficient POP-based bilirubin adsorbents for hemoperfusion therapy.

Zwitterionic microgel preservation platform for circulating tumor cells in whole blood specimen.

The immediate processing of whole blood specimen is required in circulating tumor cell-based liquid biopsy. Reliable blood specimen stabilization towards preserving circulating tumor cells can enable more extensive geographic sharing for precise rare-cell technology, but remains challenging due to the fragility and rarity of circulating tumor cells. Herein, we establish a zwitterionic magnetic microgel platform to stabilize whole blood specimen for long-term hypothermic preservation of model circulating tumor cells. We show in a cohort study of 20 cancer patients that blood samples can be preserved for up to 7 days without compromising circulating tumor cell viability and RNA integrity, thereby doubling the viable preservation duration. We demonstrate that the 7-day microgel-preserved blood specimen is able to reliably detect cancer-specific transcripts, similar to fresh blood specimens, while there are up/down expression regulation of 1243 genes in model circulating tumor cells that are preserved by commercial protectant. Mechanistically, we find that the zwitterionic microgel assembly counters the cold-induced excessive reactive oxygen species and platelet activation, as well as extracellular matrix loss-induced cell anoikis, to prevent circulating tumor cell loss in the whole blood sample. The present work could prove useful for the development of blood-based noninvasive diagnostics.

Low-Gradient Magnetophoresis of Nanospheres and Nanorods through a Single Layer of Paper.

The possible magnetophoretic migration of iron oxide nanoparticles through the cellulosic matrix within a single layer of paper is challenging with its underlying mechanism remained unclear. Even with the recent advancements of theoretical understanding on magnetophoresis, mainly driven by cooperative and hydrodynamics phenomena, the contributions of these two mechanisms on possible penetration of magnetic nanoparticles through cellulosic matrix of paper have yet been proven. Here, by using iron oxide nanoparticles (IONPs), both nanospheres and nanorods, we have investigated the migration kinetics of these nanoparticles through grade 4 Whatman filter paper with a particle retention of 20-25 µm. By performing droplet tracking experiments, the real-time stained area growth of the particle droplet on the filter paper, under the influences of a grade N40 NdFeB magnet, were recorded. Our results show that the spatial and temporal expansion of the IONP stain is biased toward the magnet and such an effect is dependent on (i) particle concentration and (ii) particle shape. The kinetics data were first analyzed by treating it as a radial wicking fluid, and later the IONP distribution within the cellulosic matrix was investigated by optical microscopy. The macroscopic flow front velocities of the stained area ranged from 259 µm/s to 16 040 µm/s. Moreover, the microscopic magnetophoretic velocity of nanorod cluster was also successfully measured as ∼214 µm/s. Findings in this work have indirectly revealed the strong influence of cooperative magnetophoresis and the engineering feasibility of paper-based magnetophoretic technology by taking advantage of magnetoshape anisotropy effect of the particles.

Zwitterionic Biomaterials.

The term "zwitterionic polymers" refers to polymers that bear a pair of oppositely charged groups in their repeating units. When these oppositely charged groups are equally distributed at the molecular level, the molecules exhibit an overall neutral charge with a strong hydration effect via ionic solvation. The strong hydration effect constitutes the foundation of a series of exceptional properties of zwitterionic materials, including resistance to protein adsorption, lubrication at interfaces, promotion of protein stabilities, antifreezing in solutions, etc. As a result, zwitterionic materials have drawn great attention in biomedical and engineering applications in recent years. In this review, we give a comprehensive and panoramic overview of zwitterionic materials, covering the fundamentals of hydration and nonfouling behaviors, different types of zwitterionic surfaces and polymers, and their biomedical applications.

Development of Organogels for Live Yarrowia lipolytica Encapsulation.

Encapsulation of cells/microorganisms attracts great attention in many applications, but current studies mainly focus on hydrophilic encapsulation materials. Herein, we develop a new class of hydrophobic and lipophilic organogels for highly efficient encapsulation of Yarrowia lipolytica, an oleaginous yeast, by a mild and nonsolvent photopolymerization method. The organogels allow free diffusion of hydrophobic molecules that oleaginous yeasts require to survive and function. Moreover, they are mechanically robust and possess favorable biocompatibility, thus providing a free-standing platform and an ideal survival environment for oleaginous Y. lipolytica encapsulation. By tuning monomer structures and cross-linking densities, the optimized organogel, Gel12-1.5%, achieves the highest viability of ∼96%. Furthermore, organogels can inhibit the cryoinjuries to oleaginous yeasts in cryopreservation, exhibiting the potential for long-term storage. It is also found that with varying alkyl lengths, the organogels show different temperature-dependent phase transition properties, which enable the rapid selection of targeted yeasts for steganography. Findings in this work provide guidance for designing biocompatible, hydrophobic, and lipophilic encapsulation materials.

A Degradable-Renewable Ionic Skin Based on Edible Glutinous Rice Gel.

Traditional wearable devices are commonly nonrecyclable and nondegradable, resulting in energy waste and environmental pollution. Here, a household degradable and renewable ionic skin based on edible glutinous rice gel is developed for a strain, temperature and salivary enzyme activity sensor. This gel depends on intermolecular and intramolecular H-bonds among amylopectin and amylose, and this presents excellent skin-like properties, including stretchability, self-healing property, and adhesion to various substrates. The glutinous rice gel-based skin sensor can be used to monitor vital signs and physiological parameters such as body temperature and heart rate. The sensor also achieves specific speech recognition and detects temperature and body micromovements, which provides the potential to reconstruct language or sensory/motor functions. More importantly, because of the excellent biocompatibility and degradability, the sensor can directly detect the activity of human salivary amylase, which is useful for diagnosing pancreas-, kidney-, and spleen-related diseases in the elderly. Finally, the raw material of ionic skin that originates from traditional grains is degradable and renewable as well as it can be used to prepare household wearable devices. Hence, this work not only extends the application of wearable electronics in daily life but also facilitates health monitoring in the elderly and improves their quality of life.

Antifouling Fibrous Membrane Enables High Efficiency and High-Flux Microfiltration for Water Treatment.

Membrane biofouling has long been a major obstacle to highly efficient water treatment. The modification of the membrane surface with hydrophilic materials can effectively enhance biofouling resistance. However, the water flux of the membranes is often compromised for the improvement of antifouling properties. In this work, a composite membrane composed of a zwitterionic hydrogel and electrospinning fibers was prepared by a spin-coating and UV cross-linking process. At the optimum conditions, the composite membrane could effectively resist the biofouling contaminations, as well as purify polluted water containing bacteria or diatoms with a high flux (1349.2 ± 85.5 L m-2 h-1 for 106 CFU mL-1 of an Escherichia coli solution). Moreover, compared with the commercial poly(ether sulfone) (PES) membrane, the membrane displayed an outstanding long-term filtration performance with a lower water flux decline. Therefore, findings in this work provide an effective antifouling modification strategy for microfiltration membranes and hold great potential for developing antifouling membranes for water treatment.

A Zwitterionic-Aromatic Motif-Based ionic skin for highly biocompatible and Glucose-Responsive sensor.

Electronic skins that can sense external stimuli have been of great significance in artificial intelligence and smart wearable devices in recent years. However, most of current skin materials are unable to achieve high biocompatibility and anti-bacterial activity, which are particularly critical to wearable sensors for neonatal/premature monitoring or tissue-interfaced biosensors (such as electronic wound dressing and smart contact lens). Herein, a zwitterionic-aromatic motif-based conductive hydrogel with electrostatic and π-π interactions is designed for the development of ionic skin sensors. The hydrogel possesses high biocompatibility, anti-bacterial activity, especially glucose-responsive property which has not been achieved by previous ionic skins. Due to its unique molecular design, the zwitterionic-aromatic skin sensor exhibits excellent mechanical properties (robust elasticity and large stretchability) and high-sensitive pressure detection (including a gentle finger touch, small water droplets, and vocal cord vibration). More importantly, aromatic motives in phenylboronic acid segments endow the skin with glucose-responsive property. This skin sensor not only shows great potential in wearable e-skins, but also possesses a promising property for the tissue-interfaced and implantable continuous-glucose-monitor biosensors such as smart wound dressing with a high demand of biocompatibility.

Amphiphilic Marine Antifouling Coatings Based on a Hydrophilic Polyvinylpyrrolidone and Hydrophobic Fluorine-Silicon-Containing Block Copolymer.

The development of environmentally friendly and highly efficient antifouling coatings is vastly desirable in the marine industry. Herein, we prepared a novel amphiphilic block copolymer that combined hydrophilic polyvinylpyrrolidone (PVP) with hydrophobic poly(1-(1H,1H,2H,2H-perfluorodecyloxy)-3-(3,6,9-trioxadecyloxy)-propan-2-yl acrylate) (PFA) and polydimethylsiloxane (PDMS). The amphiphilic copolymer (PVP-PFA-PDMS) was blended into a cross-linked PDMS matrix to form a set of controlled surface composition and surface-renewal coatings with efficient antifouling and fouling-release properties. These coatings incorporated the biofouling settlement resistance ability attributed to the hydrophilic PVP segments and the reduced adhesion strength attributed to the low surface energy of fluorine-silicon-containing segments. As expected, the coatings showed an excellent antifouling performance against bacteria and marine unicellular Navicula parva diatoms (98.1 and 98.5% of reduction, respectively) and fouling-release performance against pseudobarnacle adhesion (84.3% of reduction) compared to the pristine PDMS coating. Moreover, a higher-content PVP-based coatings presented higher ability to resist biofouling adhesion. The nontoxic antifouling coating developed in this paper hold the potential to be applied in a variety of marine industrial facilities.

MOF-Based Antibiofouling Hemoadsorbent for Highly Efficient Removal of Protein-Bound Bilirubin.

A metal-organic framework (MOF)-based antibiofouling hemoadsorbent (PCB-MIL101) was developed through a facile encapsulation of MIL-101(Cr) in zwitterionic poly carboxybetaine (PCB) hydrogel. PCB-MIL101 possessed strong mechanical strength and superior hemocompatibility, ensuring its safety in hemoperfusion applications. In addition, it showed efficient and effective adsorption toward bilirubin (BR), and its maximum adsorption capacity was ∼583 mg g-1. Moreover, due to the protection of antibiofouling PCB hydrogel, PCB-MIL101 showed ability to resist protein adsorption, thus working effectively to remove BR molecules from their binding albumin in biological solutions. The finding in this study provides a novel insight into developing MOF-based hemoadsorbents for the improvement of hemoperfusion therapies.

Metal-Organic Framework Traps with Record-High Bilirubin Removal Capacity for Hemoperfusion Therapy.

Adsorption-based hemoperfusion has been widely used to remove toxins from the blood of patients suffering acute liver failure (ALF). However, its detoxification effect has been severely hampered by the unsatisfactory adsorption performance of clinically used porous adsorbents, such as activated carbon (AC) and adsorption resin. Herein, two cage-based metal-organic frameworks (MOFs), PCN-333 (constructed from 4,4,4-s-triazine-2,4,6-triyl-tribenzoic acid (H3TATB) ligands and Al3 metal clusters) and MOF-808 (constructed from 1,3,5-benzenetricarboxylic acid (H3BTC) ligands and Zr6 metal clusters), are introduced for highly efficient hemoperfusion. They possess negligible hemolytic activity and can act as "bilirubin traps" to achieve outstanding adsorption performance toward bilirubin, a typical toxin related to ALF. Notably, PCN-333 shows a record-high adsorption capacity (∼1003.8 mg g-1) among various bilirubin adsorbents previously reported. More importantly, they can efficiently adsorb bilirubin in bovine serum albumin (BSA) solution or even in 100% fetal bovine serum (FBS) due to their high selectivity. Strikingly, the adsorption rate and capacity of PCN-333 in biological solutions are approximately four times faster and 69 times higher than those of clinical AC, respectively. Findings in this work pave a new avenue to overcome the challenge of low adsorption efficiency and capacity in hemoperfusion therapy.

Hemocompatible hemoadsorbent for effective removal of protein-bound toxin in serum.

Resin hemoperfusion is a life-saving treatment for drug intoxication or hepatic failure of patients. However, current resin adsorbents exhibit a limited hemocompatibility or low adsorption efficiency, representing a major roadblock to successful clinical applications. In this work, we developed a hemocompatible and effective hemoadsorbent based on polystyrene resin (H103) microparticles encapsulated in anti-biofouling zwitterionic poly(carboxybetaine) (PCB) hydrogels. Apart from a strong mechanical stability, this PCB-based adsorbent (PCB-H103) exhibited excellent hemocompatibility (hemolysis ratio was ∼0.64%), which was attributed to the anti-biofouling property of PCB hydrogel. In addition, it can efficiently adsorb both small and middle molecular weight molecules in phosphate-buffered saline, and the efficiencies were significantly higher than poly(ethylene glycol) methacrylate-based and poly(2-hydroxyethyl methacrylate)-based adsorbent counterparts, indicating the favorable permeability of PCB hydrogel coating. More importantly, PCB-H103 could effectively remove protein-bound toxins including phenol red and bilirubin in bovine serum albumin solution or even in 100% fetal bovine serum (FBS). In 100% FBS, the adsorption capacity of PCB-H103 towards bilirubin was 8.3 times higher than that of pristine clinical-scale resin beads. Findings in this work may provide a new strategy for the development of modern resin hemoperfusion technology.

A Robust Cotton Textile-Based Material for High-Flux Oil-Water Separation.

PDMS-based materials have been extensively studied in oil-water separation. However, their successful application is commonly limited by low efficiency, vulnerability to acid/alkali, complex processing procedures, incapability for emulsion separation, etc. Here, a highly durable and robust separation material is developed by coating PDMS-based copolymers on cotton textiles with a facile sol-gel approach. Solely driven by gravity, this new material not only can enable effective separation of oil-water mixture with a flux as high as ∼7500 L m-2 h-1 but also can separate surfactant-stabilized water-in-oil emulsion. Moreover, it remains fully functional even in the environments with high concentrations of acid, alkali, or salt. This novel and versatile strategy holds great promise to be widely used in practical applications of oil-water separation, including oil/chemical spill accidents and industrial sewage emission.

In Situ Encapsulation of Postcryopreserved Cells Using Alginate Polymer and Zwitterionic Betaine.

Currently, the state-of-the-art cryoprotectants for cell cryopreservation have bottleneck problems (such as cytotoxicity), which place enormous logistical limitations to the development of regenerative medicine. In this work, a first alginate polymer-based approach for human chondrocyte cryopreservation is reported. Combined with zwitterionic betaine, a natural osmoprotectant to offer intracellular protection, this alginate polymer-based approach can achieve ∼90% cryopreservation efficiency. Because of the biocompatibility of alginate polymer and betaine, this approach can easily retrieve the post-thaw cells without traditional multistep cryoprotectant washing procedures, which is highly favorable to cell therapy. Meanwhile, because of the feasible and mild gelation process of alginate polymer, this approach can also directly encapsulate the post-thaw cells into hydrogels without cryoprotectant removal, which is highly useful to tissue engineering. Moreover, these hydrogels exhibit tunable mechanical properties and can form variable shapes and sizes of scaffolds to inject into the patient's defect sites. After encapsulating post-thaw cells, these hydrogels can maintain high cell viability (∼90%) and normal cellular functions for at least 14 days. This work provides a step-change in cryopreservation of cells to be directly used in cell-based applications and may realize promising cellular therapy products that can integrate preservation with clinical practice.

Betaine Combined with Membrane Stabilizers Enables Solvent-Free Whole Blood Cryopreservation and One-Step Cryoprotectant Removal.

Cryopreservation of red blood cells (RBCs) is fundamentally important to modern transfusion medicine. Currently, organic solvent glycerol is utilized as the state-of-the-art cryoprotectant (CPA) for RBC cryopreservation. However, glycerol must be removed before RBC transfusion to avoid intravascular hemolysis via a time-consuming deglycerolization process with specialized equipment (e.g., ACP 215), thus limiting the clinical use of frozen RBCs. Herein, we report novel biocompatible CPA formulations combining betaine with membrane stabilizers (disaccharides or amino acids), which can achieve outstanding efficiency for RBC cryopreservation directly using whole blood without any separation process. Most importantly, because of the osmotic regulation capacity of betaine, a simple and fast one-step method can be used for CPA removal, which is significantly superior to the current multistep deglycerolization process. This work offers a promising solution for highly efficient and solvent-free RBC cryopreservation and holds great potential for improving the long-term storage and long-distance distribution of RBCs.

Facile modification of electrospun fibrous structures with antifouling zwitterionic hydrogels.

Electrospinning technology can easily produce different shaped fibrous structures, making them highly valuable to various biomedical applications. However, surface contamination of biomolecules, cells, or blood has emerged as a significant challenge to the success of electrospun devices, especially artificial blood vessels, catheters and wound dressings etc. Many efforts have been made to resist the surface non-specific biomolecules or cells adsorption, but most of them require complex pre-treatment processes, hard-to-remove metal catalysts or rigorous reaction conditions. In addition, the stability of antifouling coatings, especially in complex conditions, is still a major concern. In this work, inspired by the interpenetrating polymer network and reinforced concrete structure, an efficient and facile strategy for modifying hydrophobic electrospun meshes and tubes with antifouling zwitterionic hydrogels has been introduced. The resulting products could efficiently resist the adhesion of proteins, cells, or even fresh whole blood. Meanwhile, they could maintain the shapes and mechanical strength of the original electrospun structures. Furthermore, the hydrogel structures could retain stable in a physiological condition for at least 3 months. This paper provided a general antifouling and hydrophilicity surface modification strategy for various fibrous structures, and could be of great value for many biomedical applications where antifouling properties are critical.

Antifouling zwitterionic hydrogel coating improves hemocompatibility of activated carbon hemoadsorbent.

Activated carbon has been widely used in hemoperfusion treatments. However, its performance has been significantly compromised by their poor hemocompatibility. In this work, we developed a novel antifouling adsorbent based on zwitterionic poly-carboxybetaine (PCB) hydrogel and powdered activated carbon (PAC) to improve hemocompatibility. We found this new adsorbent (PCB-PAC) was highly stable with negligible leakage of activated carbon debris. It could efficiently resist protein adsorption and avoid any hemolysis effect. The adsorption performance of PCB-PAC for methylene blue was not influenced in a single protein solution or even in 100% fetal bovine serum (FBS), in which pristine PAC lost 50% of its adsorption ability. The isotherms results showed that the adsorption process of PCB-PAC fitted the Langmuir isotherm well, indicating that the PAC particles were homogenously distributed in the PCB hydrogel matrix. Moreover, PCB-PAC could also adsorb bilirubin molecules bound to albumin in solution, while pristine PAC showed no discernible adsorption effect. Findings in this work hold great potential to significantly improve the performance and efficiency of current extracorporeal devices for removing toxins from blood directly.

Organic selenium resin in solid phase synthesis and its application in constructing medicinally relevant small organic molecules.

Heterocyclic compounds are of high importance in constructing active drug intermediates library. The emergence of solid-phase and combinatorial chemistry has led to renewed interest in using organoselenium resins to library drug-like production. In this mini review, we summarize the construction of heterocyclic compounds libraries such as isoxazoles, oxadiazoles, triazoles, pyrimidines, pyrrolines, indolines, benzopyrans, furans etc. using organoselenium resins. And it provided efficient and practical ways for the preparation of a variety of well-defined functional heterocyclic compounds with the advantages of good yields, high purity, straightforward operations, broad range and high diversity of the products, lack of odor, and good stability of the resins, all of these give expression to green chemistry.