Biocompatible Core-Shell Microneedle Sensor Filled with Zwitterionic Polymer Hydrogel for Rapid Continuous Transdermal Monitoring.

Microneedle (MN)-based electrochemical biosensors hold promising potential for noninvasive continuous monitoring of interstitial fluid biomarkers. However, challenges, such as instability and biofouling, exist. This study proposes a design employing hollow MN to encapsulate a zwitterionic polymer hydrogel sensing layer with excellent biocompatibility and antifouling properties to address these issues. MN shell isolates the internal microporous sensing layer from subcutaneous friction, and the hydrogel filling leverages the MNs' three-dimensional structures, enabling high-dense loading of biorecognition elements. The hollow MNs are successfully fabricated from high-molecular-weight polylactic acid via drawing lithography, exhibiting sufficient strength for effective epidermis penetration. Additionally, a high-performance gold nanoconductive layer is successfully deposited inside the MN hollow channel, establishing a stable electrical connection between the polymer MN and the hydrogel sensing layer. To support the design, numerical simulations of position-based diffusive analyte solutes reveal fast-responsive electrochemical signals attributed to the high diffusion coefficient of the hydrogel and the concentrated structure of the hollow channel encapsulation. Experimental results and numerical simulations underscore the advantages of this design, showcasing rapid response, high sensitivity, long-term stability, and excellent antifouling properties. Fabricated MN sensors exhibited biosafety, feasibility, and effectiveness, with accurate and rapid in vivo glucose monitoring ability. This study emphasizes the significance of rational design, structural utilization, and micro-nanofabrication to unlock the untapped potential of MN biosensors.

Detailed Study of the Interactions between Glycopolymers in the Presence of Metal Ions through Quartz Crystal Microbalance Method.

Polymer self-assemblies driven by enthalpic interactions, such as hydrogen bonding and electrostatic interactions, exhibit distinct properties compared to those driven by hydrophobic interactions. Carbohydrate-carbohydrate interactions, which are observed in physiological phenomena, also fall under enthalpic interactions. Our group previously reported on self-assemblies of methacrylate-type glycopolymers carrying mannose units in the presence of calcium ions; however, a detailed study of these interactions was lacking. In this work, we investigated the interactions between glycopolymers using the quartz crystal microbalance (QCM) method. Our quantitative analysis revealed that the interactions between the glycopolymers were influenced by the carbohydrate structures in the side chains, the types of divalent metal ions, and the structures of the polymer main chains. Notably, the strongest interaction was observed in the combination of methacrylate-type glycopolymers carrying mannose units and calcium ions, demonstrating their potential as a driving force for polymer self-assembly.

High-Quality Three-Dimensionally Cultured Cells Using Interfaces of Diblock Copolymers Containing Different Ratios of Zwitterionic N-Oxides.

To control three-dimensional (3D) cell spheroid formation, it is well-known the surface physicochemical and mechanical properties of cell culture materials are important; however, the formation and function of 3D cells are still unclear. This study demonstrated the precise control of the formation of 3D cells and 3D cell functions using diblock copolymers containing different ratios of a zwitterionic trimethylamine N-oxide group. The diblock copolymers were composed of poly(n-butyl methacrylate) (PBMA) as the hydrophobic unit for surface coating on a cell culture dish and stabilization in water, and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) as the precursor of N-oxide. The zwitterionic N-oxide converted from 0 to 100% using PDMAEMA. The wettability and surface zeta potential varied with different ratios of N-oxide diblock copolymer-coated surfaces, and the amount of protein adsorbed in the cell culture medium decreased monotonically with increasing N-oxide ratio. 3D cell spheroid formations were observed by seeding human umbilical cord mesenchymal stem cells (hUC-MSCs) in diblock copolymer-coated flat-bottom well plates, and the N-oxide ratio was over 40%. The cells proliferated in two-dimensions (2D) and did not form spheroids when the N-oxide ratio was less than 20%. Interestingly, the expression of undifferentiated markers of hUC-MSCs was higher on surfaces that adsorbed proteins to some extent and formed 50-150 µm spheroids in the range of 40-70% of N-oxide ratio. We revealed that a moderately protein-adsorbed surface allows precise control of spheroid formation and undifferentiated 3D cells and has potential applications for high-quality spheroids in regenerative medicine and drug screening.

Explainable Prediction of Hydrophilic/Hydrophobic Property of Polymer Brush Surfaces by Chemical Modeling and Machine Learning.

Polymer informatics has attracted increasing attention as a specialized branch of material informatics. Hydrophilicity/hydrophobicity is one of the most important properties of interfaces involved in antifouling, self-cleaning, antifogging, oil/water separation, protein adsorption, and bioseparation. Establishing a quantitative structure-property relationship for the hydrophilicity/hydrophobicity of polymeric interfaces could significantly benefit from machine learning modeling. In this study, we aimed to construct machine learning models that could predict the static water contact angle (CA) as an indicator of hydrophilicity/hydrophobicity based on a data set of polymer brushes. The features of the polymer brush surfaces were numerically described using their grafted structures (thickness) and molecular descriptors derived from their chemical structures. We achieved accurate prediction and understanding of important parameters by employing appropriate molecular descriptors considering the Pearson correlation and machine learning models trained with nested cross-validation. The model interpretation by Shapley additive extension analysis indicated that the amount of partial polar/nonpolar structure in the molecule as well as the averaged hydrophobicity represented by MolLogP plays an important role in determining the CA. Moreover, the model can predict the CAs of polymer brushes composed of chemical structures that are not present in existing databases. The CA values of the hypothetical polymer brushes are predicted.

Stability Enhancement by Hydrophobic Anchoring and a Cross-Linked Structure of a Phospholipid Copolymer Film for Medical Devices.

Surface modification using zwitterionic 2-methacryloyloxyethylphosphorylcholine (MPC) polymers is one of the most reasonable ways to prepare medical devices that can suppress undesired biological reactions such as blood coagulation. Usable MPC polymers are hydrophilic and water soluble, and their surface modification strategy involves exploiting the copolymer structures by adding physical or chemical bonding moieties. In this study, we developed copolymers composed of MPC, hydrophobic anchoring moiety, and chemical cross-linking unit to clarify the role of hydrophobic interactions in achieving biocompatible and long-term stable coatings. The four kinds of MPC copolymers with cross-linking units, such as 3-methacryloxypropyl trimethoxysilane (MPTMSi), and four different hydrophobic anchoring moieties, such as 3-(methacryloyloxy)propyltris(trimethylsiloxy)silane (MPTSSi) named as PMMMSi, n-butyl methacrylate (BMA) as PMBSi, 2-ethylhexyl methacrylate (EHMA) as PMESi, and lauryl methacrylate as PMLSi, were synthesized and coated on polydimethylsiloxane, polypropylene (PP), and polymethyl pentene. These copolymers were uniformly coated on the substrate materials PP and poly(methyl pentene) (PMP), to achieve hydrophilic and electrically neutral coatings. The results of the antibiofouling test showed that PMBSi repelled the adsorption of fluorescence-labeled bovine serum albumin the most, whereas PMLSi repelled it the least. Notably, all four copolymers suppressed platelet adhesion similarly. The variations in protein adsorption quantities among the four copolymer coatings were attributed to their distinct swelling behaviors in aqueous environments. Further investigations, including 3D scanning force microscopy and neutron reflectivity measurements, revealed that the PMLSi coating exhibited a higher water intake under aqueous conditions in comparison to the other coatings. Consequently, all copolymer coatings effectively prevented the invasion of platelets but the proteins penetrated the PMLSi network. Subsequently, the dynamic stability required to induce shear stress was evaluated using a circulation system. The results demonstrated that the PMMMSi and PMLSi coatings on PMP and PP exhibited exceptional platelet repellency and maintained high stability during circulation. This study highlights the potential of hydrophobic moieties to improve hemocompatibility and stability, offering potential applications in medical devices.

Enzyme stability in polymer hydrogel-enzyme hybrid nanocarrier containing phosphorylcholine group.

Enzymes are biological catalysts with good biocompatibility and high efficiency and have been widely used in many fields, such as wastewater treatment, biosensors, and the medical industry. However, their inherently low stability under conditions of practical use limits further applications. Zwitterionic polymers possessing a pair of oppositely charged groups in their repeating units can increase protein stability because of their good biocompatibility and high water content. In this study, zwitterionic copolymer nanogels comprising poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-methacrylic acid-N-hydroxy succinimide ester (MNHS)) (PMS) were synthesized via reversible addition-fragmentation chain-transfer polymerization (RAFT). ß-Galactosidase (ß-gal) was post-modified within zwitterionic polymer nanogels with a covalently-bound spacer and the activity was compared with that of directly immobilized ß-gal and free ß-gal. Compared with direct immobilization, covalent immobilization with a spacer could reduce the structural change of ß-gal, as confirmed by the circular dichroism spectra. Although the activity of ß-gal decreased after immobilization, the hybrids of the ß-gal immobilized nanogels, termed hybrid nanogel-enzymes, demonstrated superior stability compared to the free enzymes. The hybrid nanogel-enzymes maintained their function against inactivation by organic solvents and proteinases owing to their high water content, anti-biofouling properties, and limited mass transfer. They can also withstand protein aggregation at high temperatures and maintain their activity. Compared to direct immobilization, immobilization with a spacer resulted in a dramatic increase in the enzyme activity and a slight decrease in the stability. These results indicate that polymer nanogels containing phosphorylcholine units are promising materials for enzyme immobilization, expanding the scope of enzyme applications.

Microfluidic electrochemical biosensors: tools for advancing the sustainable development goals.

New technologies can help to achieve the sustainable development goals (SDGs) of the United Nations. We discuss the contribution of microfluidic electrochemical biosensors to advancing the SDGs. These sensors can be applied in various fields given their low cost, self-powering ability, environmental compatibility, ease of use, and small sample volume requirements.

Antimicrobial Peptide Assembly on Zwitterionic Polymer Films to Slow Down Biofilm Formation.

Formation of biofilms on equipment used in various fields, such as medicine, domestic sanitation, and marine transportation, can cause serious problems. The use of antibiofouling and bactericidal modifications is a promising strategy for inhibiting bacterial adhesion and biofilm formation. To further enhance the antibiofilm properties of a surface, various combinations of bactericidal modifications alongside antibiofouling modifications have been developed. Optimization of the arrangements of antimicrobial peptides on the antibiofouling surface would allow us to design longer-life antibiofilm surface modifications. In this study, a postmodification was conducted with different design using the antimicrobial peptide KR12 on an antibiofouling copolymer film consisting of 2-methacryloyloxyethyl phosphorylcholine, 3-methacryloxypropyl trimethoxysilane, and 3-(methacryloyloxy) propyl-tris(trimethylsilyloxy) silane. The distance of KR12 from the film was adjusted by combining different lengths of poly(ethylene glycol) (PEG) spacers (molecular weights are 2000 and 5000). The density of KR12 was ranged from 0.06 to 0.22 nm-2. When these modified surfaces were exposed to a nutrient-rich TSB suspension, the bacterial area formed by E. coli covered 5-127% of the original copolymer film. We found that a significant distance between the bactericidal and antibiofouling modifications, along with a higher density of bactericidal modifications, slows down the biofilm formation.

Preparation of cellular membrane-mimicking glycopolymer interfaces by a solvent-assisted method on QCM-D sensor chips and their molecular recognition.

Carbohydrate-based membranes that show molecular recognition ability are interesting mimics of biointerfaces. Herein, we prepared glycopolymer membranes on QCM-D sensor chips using a solvent-assisted method and investigated their interactions with a target lectin. The membrane containing the glycopolymer with a random arrangement of the carbohydrate units adsorbed more lectin than that containing the glycopolymer with an organized block of carbohydrate units.

Superior antibacterial surfaces using hydrophilic, poly(MPC) and poly(mOEGMA) free chains of amphiphilic block copolymer for sustainable use.

Surface modification of electrically neutral hydrophilic polymers is one of the most promising methods for preventing biofouling and biological contamination by proteins and bacteria. Surface modification of inorganic materials such as silica-based glass can render them more durable and thus help in achieving the sustainable development goals. This study reports a novel method for the simple and effective surface modification of glass surfaces with amphiphilic block copolymers possessing the silane coupling segment composed of 3-(methacryloyloxy)propyltris (trimethylsilyloxy) silane and 3-methacryloxypropyltrimethoxysilane. The ability of hydrophilic segments composed of either 2-methacryloyloxyethyl phosphorylcholine (MPC) or poly(ethylene glycol) methyl ether methacrylate (mOEGMA) to prevent bacterial adhesion was investigated. The target block copolymers were prepared by reversible addition-fragmentation chain transfer polymerization and the monomer units of the hydrophilic segments were controlled to be either 120 or 160. The polymers were modified on the substrate by dip-coating. Contact angle measurements indicated that the block copolymer with the PMPC hydrophilic segment formed a hydrophilic surface without pre-hydration, while those with the PmOEGMA hydrophilic segment-coated surface became hydrophilic upon immersion in water. The block copolymer-coated surfaces decreased S. aureus adhesion, and a significant reduction was observed with the MPC-type block copolymer. The following surface design guidelines were thus concluded: (1) the block copolymer is superior to the random copolymer and (2) increasing the hydrophilic segment length further decreases bacterial adhesion.

Adhesion preference of the sticky bacterium Acinetobacter sp. Tol 5.

Gram-negative bacterium Acinetobacter sp. Tol 5 exhibits high adhesiveness to various surfaces of general materials, from hydrophobic plastics to hydrophilic glass and metals, via AtaA, an Acinetobacter trimeric autotransporter adhesin Although the adhesion of Tol 5 is nonspecific, Tol 5 cells may have prefer materials for adhesion. Here, we examined the adhesion of Tol 5 and other bacteria expressing different TAAs to various materials, including antiadhesive surfaces. The results highlighted the stickiness of Tol 5 through the action of AtaA, which enabled Tol 5 cells to adhere even to antiadhesive materials, including polytetrafluoroethylene with a low surface free energy, a hydrophilic polymer brush with steric hindrance, and mica with an ultrasmooth surface. Single-cell force spectroscopy as an atomic force microscopy technique revealed the strong cell adhesion force of Tol 5 to these antiadhesive materials. Nevertheless, Tol 5 cells showed a weak adhesion force toward a zwitterionic 2-methacryloyloxyethyl-phosphorylcholine (MPC) polymer-coated surface. Dynamic flow chamber experiments revealed that Tol 5 cells, once attached to the MPC polymer-coated surface, were exfoliated by weak shear stress. The underlying adhesive mechanism was presumed to involve exchangeable, weakly bound water molecules. Our results will contribute to the understanding and control of cell adhesion of Tol 5 for immobilized bioprocess applications and other TAA-expressing pathogenic bacteria of medical importance.

Bactericidal Ability of Well-Controlled Cationic Polymer Brush Surfaces and the Interaction Analysis by Quartz Crystal Microbalance with Dissipation.

In this study, cationic poly(2-(methacryloyloxy)ethyl) trimethylammonium chloride) (PMTAC) brush surfaces were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP), and their properties were systematically investigated to discuss the factors affecting their bactericidal properties and interactions with proteins. Model equations for the analysis of electrophoretic behaviors were considered for accurate parameter estimation to indicate the charge density at the interface. The zeta potential dependency of the PMTAC brushes was successfully analyzed using Smolchowski's equation and the Gouy-Chapman model, which describes the diffusive electric double layer. The analysis of the quartz crystal microbalance with dissipation (QCM-D) indicated that the electrostatic interaction promoted protein adsorption, with a large quantity of a negatively charged protein, bovine serum albumin (BSA), being adsorbed. The bactericidal efficiency of the high-graft-density polymer brush (0.45 chains nm-2) was higher than that of the low-graft-density polymer brush (0.06 chains nm-2). To investigate the mechanism of this phenomenon, we applied the dissipation change (ΔD) of QCM-D analysis. The BSA was likewise adsorbed when the brush structure was changed; however, the negative ΔD indicated that the BSA-adsorbed, high-graft-density PMTAC brush became a rigid state. In the bacteria culture media, the behaviors were the same as BSA adsorption, and the high-graft-density polymer brush was also estimated to be more rigid than the low-graft-density polymer brush. Moreover, for S. aureus adhesion after incubating in TSB, a small slope of ΔD/ΔF plots considered initial adsorption of bacteria on the high-graft-density polymer brush strongly interacted compared to that of the low-graft-density polymer brush. The scattered value of the slope of ΔD/ΔF on the high-graft-density polymer brush was considered to be due to the dead bacteria between the bacteria and the polymer brush interface. These investigations for a well-defined cationic polymer brush will contribute to the design of antibacterial surfaces.

An automatic immuno-microfluidic system integrating electrospun polystyrene microfibrous reactors for rapid detection of salivary cortisol.

Conventional competitive enzyme-linked immunosorbent assay (ELISA) to measure the cortisol level in body fluid consumes a large amount of time, owing to complicated operations involved and requirement for precise control of reagent addition. We developed an automatic microfluidic system to detect salivary cortisol rapidly, and an electrospun polystyrene (PS) microfiber-based reactor providing considerable binding sites for antibody immobilization, thus resolving the time limitations of competitive ELISA. Cortisol sample, horseradish peroxidase (HRP)-conjugated cortisol, and 3,3',5,5'-tetramethylbenzidine (TMB) substrate were delivered to the PS reactor from containers in sequence by pumps automatically. The color variation due to oxidized TMB complex reflects the cortisol concentration level measured using an RGB phototransistor. In addition, the entire procedure from sample introduction to obtaining the photocurrent took only 15 min. This system can be implemented to quantify cortisol from 0.37 ng/mL to 30 ng/mL, and the limit of detection was estimated at 0.37 ng/mL.

Multi-Armed Star-Shaped Block Copolymers of Poly(ethylene glycol)-Poly(furfuryl glycidol) as Long Circulating Nanocarriers.

Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization degree of each block was controlled by adjusting the feeding ratio of a furfuryl glycidyl ether and ethylene oxide. The size of the series of block copolymers was found to be less than 10 nm in DMF. In water, the polymers showed sizes larger than 20 nm, which can be related to the association of the polymers. The star-shaped block copolymers effectively loaded maleimide-bearing model drugs in their core-forming segment with the Diels-Alder reaction. These drugs were rapidly released upon heating via a retro Diels-Alder step. When the star-shaped block copolymers were injected intravenously in mice, they showed prolonged blood circulation, with more than 80% of the injected dose remaining in the bloodstream at 6 h after intravenous injection. These results indicate the potential of the star-shaped PFG-PEG block copolymers as long-circulating nanocarriers.

Cell Spheroid Formation on the Surface of Multi-Block Copolymers Composed of Poly(2-methoxyethyl acrylate) and Polyethylene Glycol.

3D structured cells have great drug screening potential because they mimic in vivo tissues better than 2D cultured cells. In this study, multi-block copolymers composed of poly(2-methoxyethyl acrylate) (PMEA) and polyethylene glycol (PEG) are developed as a new kind of biocompatible polymers. PEG imparts non-cell adhesion while PMEA acts as an anchoring segment to prepare the polymer coating surface. The multi-block copolymers show higher stability in water than PMEA. A specific micro-sized swelling structure composed of a PEG chain is observed in the multi-block copolymer film in water. A single NIH3T3-3-4 spheroid is formed in 3 h on the surface of the multi-block copolymers with 8.4 wt% PEG. However, at a PEG content of 0.7 wt%, spheroid formed after 4 days. The adenosine triphosphate (ATP) activity of cells and the internal necrotic state of the spheroid change depending on PEG loading in the multi-block copolymers. As the formation rate of cell spheroid on low-PEG-ratio multi-block copolymers is slow, internal necrosis of cell spheroid is less likely to occur. Consequently, the cell spheroid formation rate by changing the PEG chain content in multi-block copolymers is successfully controlled. These unique surfaces are suggested to be useful for 3D cell culture.

Miniaturized and multiplexed high-content screening of drug and immune sensitivity in a multichambered microwell chip.

Here, we present a methodology based on multiplexed fluorescence screening of two- or three-dimensional cell cultures in a newly designed multichambered microwell chip, allowing direct assessment of drug or immune cell cytotoxic efficacy. We establish a framework for cell culture, formation of tumor spheroids, fluorescence labeling, and imaging of fixed or live cells at various magnifications directly in the chip together with data analysis and interpretation. The methodology is demonstrated by drug cytotoxicity screening using ovarian and non-small cell lung cancer cells and by cellular cytotoxicity screening targeting tumor spheroids of renal carcinoma and ovarian carcinoma with natural killer cells from healthy donors. The miniaturized format allowing long-term cell culture, efficient screening, and high-quality imaging of small sample volumes makes this methodology promising for individualized cytotoxicity tests for precision medicine.

Silver-loaded carboxymethyl cellulose nonwoven sheet with controlled counterions for infected wound healing.

Carboxymethyl cellulose (CMC) is a promising material for moist wound healing, and silver loading onto CMC has been examined for anti-bacterial activity. In this study, we developed silver-loaded CMC nonwoven sheets with different counterions, namely sodium CMC (CMC-Na/Ag) and partially protonated CMC (CMC-H/Ag), to examine their anti-bacterial and wound-healing properties. Owing to the presence of counter protons, CMC-H/Ag showed slower water adsorption, dissolution, and Ag release than CMC-Na/Ag. In addition, CMC-H/Ag and CMC-Na/Ag exhibited differences in anti-bacterial activities in shake-flask and inhibition zone tests in vitro. An in vivo experiment using a pressure ulcer mouse model with Pseudomonas aeruginosa infection showed that CMC-Na/Ag significantly accelerated wound healing compared to CMC-H/Ag and a commercially available Ag-loaded CMC nonwoven sheet, Aquacel Ag. These results suggest the importance of controlling CMC counterions and the therapeutic potential of the developed product as a wound dressing.

Cell Adhesion and Migration on Thickness Gradient Bilayer Polymer Brush Surfaces: Effects of Properties of Polymeric Materials of the Underlayer.

In the field of tissue engineering and biomaterials, controlling the surface properties and mechanical properties of scaffold materials is crucial and has attracted much attention. Here, two types of bilayer polymer brushes composed of a hydrophilic underlying layer and a cationic surface layer [made of poly(2-aminoethyl methacrylate)] with a thickness gradient were prepared by surface-initiated atom-transfer radical polymerization. To investigate the influence of the stiffness as a mechanical property of the polymer brush on cell behavior, the underlayer was prepared from either 2-methacryloyloxyethyl phosphorylcholine or oligo(ethylene glycol) methyl ether methacrylate, with the bilayers designated as gradient poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(2-aminoethyl methacrylate) [grad-pMbA] and gradient poly(oligo[ethylene glycol] methyl ether methacrylate)-block-poly(2-aminoethyl methacrylate) [grad-pEGbA], respectively. Characterization of these surfaces was performed by spectroscopic ellipsometry, X-ray reflectivity, and determination of the zeta potential, static contact angle, and force curve. These diblock copolymer brushes with a thickness gradient helped to distinguish the effects of the mechanical and surface properties of the brushes on cell behavior. The attachment and motility of L929 fibroblasts and epithelial MCF 10A cells on the fabricated brushes were then assessed. L929 cells had a round shape on the thin surface layer of grad-pMbA and spread well on thicker areas. In contrast, MCF 10A cells spread well in areas of any thickness of either grad-pMbA or grad-pEGbA. Single MCF 10A cells migrated randomly on grad-pMbA, whereas grouped cells started to climb up along the thickness gradient of grad-pMbA. In contrast, both single and grouped MCF 10A cells migrated randomly on grad-pEGbA. These thickness gradient diblock copolymer brushes are simple, reproducible, and reasonable platforms that can facilitate practical applications of biomaterials, for example, in tissue engineering and biomaterials.

Design of biointerfaces composed of soft materials using controlled radical polymerizations.

Soft interface materials have an immense potential for the improvement of biointerfaces, which are the interface of biological and artificially designed materials. Controlling the chemical and physical structures of the interfaces at the nanometer level plays an important role in understanding the mechanism of the functioning and its applications. Controlled radical polymerization (CRP) techniques, including atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain-transfer (RAFT) polymerization, have been developed in the field of precision polymer chemistry. It allows the formation of well-defined surfaces such as densely packed polymer brushes and self-assembled nanostructures of block copolymers. More recently, a novel technique to prepare polymers containing biomolecules, called biohybrids, has also been developed, which is a consequence of the advancement of CRP so as to proceed in an aqueous media with oxygen. This review article summarizes recent advances in CRP for the design of biointerfaces.

pH-Responsive Water-Soluble Polymer Carriers for Cell-Selective Metabolic Sialylation Labeling.

Cell-surface sialic acids can be metabolically labeled and subsequently modified using bioorthogonal chemistry. The method has great potential for targeted therapy and imaging; however, distinguishing the sialylation of specific cells remains a major challenge. Here, we described a cell-selective metabolic sialylation labeling strategy based on water-soluble polymer carriers presented with pH-responsive N-azidoacetylmannosamine (ManNAz) release. 2-Methacryloyloxyethyl phosphorylcholine contributed to increased water solubility and reduced nonspecific attachment to cells. Lactobionic acid residues, used for cell selectivity, recognized overexpressed receptors on target hepatoma cells and mediated cellular internalization. ManNAz caged by acidic pH-responsive carbonated ester linkage on the polymer was released inside target cells and expressed as azido sialic acid. Additionally, longer copolymer carriers enhanced the metabolic labeling efficiency of sialylation. This approach provides a platform for cell-selective labeling of sialylation and can be applied to high-resolution bioimaging and targeted therapy.