Integrating Metabolic Oligosaccharide Engineering and SPAAC Click Chemistry for Constructing Fibrinolytic Cell Surfaces.

To effectively solve the problem of significant loss of transplanted cells caused by thrombosis during cell transplantation, this study simulates the human fibrinolytic system and combines metabolic oligosaccharide engineering with strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry to construct a cell surface with fibrinolytic activity. First, a copolymer (POL) of oligoethylene glycol methacrylate (OEGMA) and 6-amino-2-(2-methylamido)hexanoic acid (Lys) was synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization, and the dibenzocyclooctyne (DBCO) functional group was introduced into the side chain of the copolymer through an active ester reaction, resulting in a functionalized copolymer DBCO-PEG4-POL with ε-lysine ligands. Then, azide functional groups were introduced onto the surface of HeLa model cells through metabolic oligosaccharide engineering, and DBCO-PEG4-POL was further specifically modified onto the surface of HeLa cells via the SPAAC "click" reaction. In vitro investigations revealed that compared with unmodified HeLa cells, modified cells not only resist the adsorption of nonspecific proteins such as fibrinogen and human serum albumin but also selectively bind to plasminogen in plasma while maintaining good cell viability and proliferative activity. More importantly, upon the activation of adsorbed plasminogen into plasmin, the modified cells exhibited remarkable fibrinolytic activity and were capable of promptly dissolving the primary thrombus formed on their surfaces. This research not only provides a novel approach for constructing transplantable cells with fibrinolytic activity but also offers a new perspective for effectively addressing the significant loss of transplanted cells caused by thrombosis.

PEG-functionalized aliphatic polycarbonate brushes with self-polishing dynamic antifouling properties.

Hydrophilic antifouling polymers provide excellent antifouling effects under usual short-term use conditions, but the long-term accumulation of contaminants causes them to lose their antifouling properties. To overcome this drawback, surface-initiated ring-opening graft polymerization (SI-ROP) was performed on the surface of the material by applying the cyclic carbide monomer 4'-(fluorosulfonyl)benzyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC), which contains a sulfonylfluoride group on the side chain, followed by a "sulfur(IV)-fluorine exchange" (SuFEx) post click modification reaction to link the hydrophilic polyethylene glycol (PEG) to the polyFMC (PFMC) brush, and a novel antifouling strategy for self-polishing dynamic antifouling surfaces was developed. The experimental results showed that the antifouling surface could effectively prevent the adsorption of proteins such as bovine serum albumin (BSA, ∼96.4%), fibrinogen (Fg, ∼87.8%) and lysozyme (Lyz ∼69.4%) as well as the adhesion of microorganisms such as the bacteria Staphylococcus aureus (S. aureus) (∼87.5%) and HeLa cells (∼67.2%). Moreover, the enzymatically self-polished surface still has excellent antifouling properties. Therefore, this modification method has potential applications in the field of biosensors and novel antifouling materials.

Janus-type ionic conductive gels based on poly(N,N-dimethyl)acrylamide for strain/pressure sensors.

Strain/pressure sensors with high sensitivity and a wide operation range have broad application prospects in wearable medical equipment, human-computer interactions, electronic skin, and so on. In this work, based on the different solubilities of Zr4+ in the aqueous phase and the hydrophobic ionic liquid [BMIM][Tf2N], we used N,N-dimethylacrylamide (DMA) as a vinyl monomer to prepare a Janus-type ionic conductive gel with one-sided adhesion through "one-step" UV irradiation polymerization. The Janus-type gel has satisfactory mechanical properties (tensile strength: 217.06 kPa, elongation at break: 1121.01%), electrical conductivity (conductivity: 0.10 S m-1), one-sided adhesion (adhesion strength to glass: 72.35 kPa) and antibacterial properties. The sensor based on the Janus gel can be used not only for real-time monitoring of strain changes caused by various movements of the human body (such as finger bending, muscle contraction, smiling, and swallowing) but also for real-time monitoring of pressure changes (such as pressing, water droplets, and writing movements). Therefore, based on the simplicity of this method for constructing Janus-type ionic conductive gels and the excellent electromechanical properties of the prepared gel, we believe that the method provided in this study has broad application prospects in the field of multifunctional wearable sensors.

Transparent ionic conductive elastomers with high mechanical strength and strong tensile properties for strain sensors.

Stretchable ionic conductive elastomers have been extensively studied due to their great application potential in the fields of sensors, batteries, capacitors and flexible robots. However, it is still challenging to prepare multifunctional ionic conductive elastomers with high mechanical strength and excellent tensile properties by a green and efficient method. In this study, we prepared PDES-DMA ionic conductive elastomers by a "one step" rapid in situ polymerization of AA/ChCl-type polymerizable deep eutectic solvents (PDES) and N,N-dimethylacrylamide (DMA) under ultraviolet (UV) irradiation. In addition to the characteristics of high mechanical strength (tensile strength of 9.27 MPa) and excellent tensile properties (elongation at break of 1071%), the PDES-DMA elastomer also has high transparency (>80%), strong self-adhesion (adhesion strength with glass surface 133.8 kPa) and self-healing properties. In addition, sensors based on the ionic conductive elastomer can be used to detect human movements such as finger, wrist, elbow, ankle and knee bending. Considering the convenience of the preparation method and the excellent versatility of the prepared PDES-DMA ionic conductive elastomer, we believe that the method proposed in this study has potential application prospects in the field of flexible electronics.

Poly(N,N-dimethyl)acrylamide-based ion-conductive gel with transparency, self-adhesion and rapid self-healing properties for human motion detection.

Flexible strain sensors have been extensively studied for their potential value in monitoring human activity and health. However, it is still challenging to develop multifunctional flexible strain sensors with simultaneously high transparency, strong self-adhesion, fast self-healing and excellent tensile properties. In this study, we used N,N-dimethylacrylamide (DMA) in the imidazolium-based ionic liquid 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl] imide ([BMIM][Tf2N]) for "one-step" UV irradiation. A poly(N,N-dimethyl)acrylamide (PDMA) ion-conductive gel was prepared by site polymerization. Based on the good compatibility between PDMA and ionic liquid, the prepared ion-conductive gel has good transparency (∼90%), excellent stretchability (1080%), strong self-adhesion (67.57 kPa), fast self-healing (2 s at room temperature) and great antibacterial activity (∼99% bacterial killing efficiency). Moreover, the strain sensor based on the PDMA ion-conductive gel has good electromechanical performance and can detect different human motions. Based on the simple and easy-to-operate preparation method and the endowed multifunctionality of the PDMA ion-conductive gel, it has broad application prospects in the field of flexible electronic devices.

Introducing SuFEx click chemistry into aliphatic polycarbonates: a novel toolbox/platform for post-modification as biomaterials.

As a biodegradable and biocompatible biomaterial, aliphatic polycarbonates (APCs) have attracted substantial attention in terms of post-polymerization modification (PPM) for functionalization. A strategy for the introduction of sulfur(VI)-fluoride exchange (SuFEx) click chemistry into APCs for PPM is proposed for the first time in this work. 4'-(Fluorosulfonyl)benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC) was designed as a SuFEx clickable cyclic carbonate for APCs via ring-opening polymerization (ROP), and an operational and nontoxic synthetic route was achieved. FMC managed to undergo both ROP and PPM through the SuFEx click chemistry organocatalytically without constraining or antagonizing each other, using 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) as a co-organocatalyst here. Its ROP was systematically investigated, and density functional theory (DFT) calculations were performed to understand the acid-base catalytic mechanism in the anionic ROP. Exploratory investigations into PPM by SuFEx of poly(FMC) were conducted as biomaterials, and the one-pot strategies to achieve both ROP and SuFEx were confirmed.

Preparing Well-Defined Polyacrylamide-b-polycarbonate by Integrating Photoiniferter Polymerization and TBD-Catalyzed ROP.

The dual-initiator technique allows the polymerization of different monomers from orthogonal polymerization mechanisms to obtain block copolymers (BCPs). In this study, it is attempted to combine photoiniferter living free radical polymerization and organocatalytic ring-opening polymerization (ROP) to design a hydroxyl-functionalized carbamodithioate, i.e., 4-(hydroxymethyl)benzyl diethylcarbamodithioate (HBDC), which can integrate photoiniferter polymerization of acrylamide monomers and ROP of cyclic carbonates. As a proof of concept, the monomer applicability is further extended to acrylates and lactones. The results confirm that the two polymerization systems are experimentally compatible in a stepwise sequence as well as in a simultaneous one-pot process to synthesize BCPs. It is reasonable to assume that HBDC can allow for simple and efficient one-pot access to well-defined BCPs from a larger range of monomers, which is more advantageous from the operational, economical, and environmental points of view.

Oxygen-Demanding Photocontrolled RAFT Polymerization Under Ambient Conditions.

A photocontrolled reversible addition-fragmentation chain transfer (RAFT) process is developed by initiating polymerization through a 1,3-diaminopropane-triethylborane (DAPTB)-diphenyl iodonium salt (Ph2 I+ ) complex (DAPTB/Ph2 I+ ) under ambient temperature and atmospheric conditions. Upon demand, this air-stable DAPTB/Ph2 I+ complex is photolyzed to liberate a reactive triethylborane that consumes atmospheric oxygen and generates ethyl radicals, which initiate and mediate RAFT polymerization. Controlled RAFT polymerization is thus achieved without any prior deoxygenation using a novel RAFT chain transfer agent, BP-FSBC, which contains both benzophenone and sulfonyl fluoride moieties. Furthermore, the kinetics of polymerization reveal that the reaction process is rapid, and well-defined polymers are produced by a 61% conversion of 2-hydroxyethyl acrylate (HEA) within 7 min and 77% conversion of N,N-dimethylacrylamide (DMA) within 10.5 min. The temporal and spatial control of this photopolymerization is also demonstrated by an "on/off" switch of UV irradiation and a painting-on-a-surface approach, respectively. In addition, active chain ends are demonstrated by preparing block copolymers by chain extension and click sulfur(VI)-fluoride exchange postreaction using RAFT-derived macrochain transfer agents.

A novel Y-shaped photoiniferter used for the construction of polydimethylsiloxane surfaces with antibacterial and antifouling properties.

The simultaneous introduction of two new functionalities into the same polymeric substrate under mild reaction conditions is an interesting and important topic. Herein, dual-functional polydimethylsiloxane (PDMS) surfaces with antibacterial and antifouling properties were conveniently developed via a novel Y-shaped asymmetric dual-functional photoiniferter (Y-iniferter). The Y-iniferter was initially immobilized onto the PDMS surface by radical coupling under visible light irradiation. Afterwards, poly(2-hydroxyethyl methacrylate) (PHEMA) brushes and antibacterial ionic liquid (IL) fragments were simultaneously immobilized on the Y-iniferter-modified PDMS surfaces by combining the sulfur(VI)-fluoride exchange (SuFEx) click reaction and UV-photoinitiated polymerization. Experiments using E. coli as a model bacterium demonstrated that the modified PDMS surfaces had both the expected antibacterial properties of the IL fragments and the excellent antifouling properties of PHEMA brushes. Furthermore, the cytotoxicity of the modified PDMS surfaces to L929 cells was examined in vitro with a CCK-8 assay, which showed that the modified surfaces maintained excellent cytocompatibility. Briefly, this strategy of constructing an antibacterial and antifouling PDMS surface has the advantages of simplicity and convenience and might inspire the construction of diverse dual-functional surfaces by utilizing PDMS more effectively.

Synthesis and antifouling performance of tadpole-shaped poly(N-hydroxyethylacrylamide) coatings.

Linear poly(N-hydroxyethylacrylamide) (PHEAA) is regarded as one of the most promising antifouling materials because of its excellent antifouling properties and good hemocompatibility. However, the antifouling performance of topological PHEAAs remains largely unknown. Herein, the preparation of antifouling surfaces based on a tadpole-shaped PHEAA coating is reported for the first time, and how the tadpole-shaped PHEAA architecture affects antifouling performance is investigated. It is shown that the tadpole-shaped PHEAA-modified surfaces exhibit better antifouling performance than linear copolymer precursor-modified surfaces with identical molar masses and chemical compositions. This may be primarily attributed to the presence of cyclic PHEAA head chain segments in the tadpole-shaped PHEAA copolymer, and the absence of interchain entanglements can facilitate the formation of smoother and densely packed grafts, which result in better antifouling properties.

Reactive films fabricated using click sulfur(vi)-fluoride exchange reactions via layer-by-layer assembly.

The fabrication of multilayer assemblies from polymeric compounds is an important tool for meeting the increasing demand in functional surface-based research areas. In this report, a novel and efficient approach for the fabrication of polymer multilayered films using the "sulfur(vi)-fluoride exchange" (SuFEx) click reaction is described. To develop this approach, a sulfonyl fluoride-rich polymer, poly(N-vinyl-2-pyrrolidone)-co-poly(3-(fluorosulfonyl)-propyl methacrylate) (PVP-co-PFPM), and a silyl ether-rich polymer, tert-butyldimethylsilyl-modified polyvinyl alcohol (PVA-TBDMS), were chosen as model polymers. Through step-and-repeat spin-assisted layer-by-layer (LbL) procedures, multilayer films are then generated in which all the individual layers are covalently bonded to each other. Furthermore, multilayer films containing free sulfonyl fluoride groups can be readily functionalized via the SuFEx click reaction to tailor the properties of the films for various potential applications. As a proof-of-concept, using the (PVA-TBDMS/PVP-co-PFPM)5 multilayer as a model film, the utility of the residual sulfonyl fluoride functionality for biomedical applications, such as H2S biosensors and antibiofouling and antibacterial films, is demonstrated.

Tri-functional platform for the facile construction of dual-functional surfaces via a one-pot strategy.

The scope of simultaneously introducing two new functionalities into the same polymeric substrate is largely limited to facile grafting approaches. Here, we designed a novel tri-functional platform and facilely constructed dual-functional surfaces in one pot by combining the "sulfur(vi)-fluoride exchange" (SuFEx) click reaction, photoinitiated polymerization and benzophenone photochemistry.

Chemical Surface Modification of Polymeric Biomaterials for Biomedical Applications.

This review focuses on the attachment of polymer brushes to polymeric biomaterial substrates by chemical surface modification methods for biomedical applications. In the first part of this paper, a general introduction to the synthesis of polymer brushes is given. Thereafter, a comprehensive overview of recent work on the chemical surface modification of polymeric biomaterials, with a focus on "grafting-to," "grafting-from," and "grafting-through" strategies, is provided. Finally, some representative cutting-edge biomedical applications of modified polymeric biomaterials, mainly including antifouling materials and biocompatible materials, are highlighted. On the basis of this literature study, a perspective on future trends in this field is provided.

Enhancement of Bactericidal Activity via Cyclic Poly(cationic liquid) Brushes.

In addition to extensive studies of conventional linear poly(ionic liquids) (PILs), exploration of the effects of PIL topology, especially cyclic architecture, on bactericidal properties will expand the design possibilities for the development of excellent antibacterial surfaces. Herein, the preparation of antibacterial surfaces based on cyclic PIL brushes is reported for the first time and how the cyclic PIL architecture affects bactericidal activity is investigated. It is shown that the cyclic architecture imparted PIL brushes with enhanced bactericidal activity, achieving only 1.7% of bacterial viable percentage against gram-negative Escherichia coli using Live/Dead staining methods, compared to 6.6% for the corresponding linear PIL brushes. The enhanced bactericidal activity is also validated by the direct observation of scanning electron microscopy and a colony counting assay. Further mechanism studies reveal that the substantially different morphologies of cyclic aggregates and altered surface charge density induced by the cyclic PIL architecture can account for the enhanced bactericidal activity.

Efficient Heterodifunctional Unimolecular Ring-Closure Method for Cyclic Polymers by Combining RAFT and SuFEx Click Reactions.

A novel ring-closure strategy for cyclic polymers by combining reversible addition-fragmentation chain transfer polymerization (RAFT) and the sulfur(VI)-fluoride exchange (SuFEx) click reaction is presented. Herein, a new heterodifunctional trithiocarbonate RAFT agent, 2-((tert-butyldimethylsilyl)oxy)ethyl (4-(fluorosulfonyl)benzyl) carbonotrithioate (TBDMS-FSBCT), containing both tert-butyldimethylsilyl ether and sulfonyl fluoride moieties, is developed. The polymerization behavior of TBDMS-FSBCT is first demonstrated by a standard RAFT polymerization procedure for two types of vinyl monomers, N-isopropylacrylamide (NIPAAm) (conjugated vinyl monomer) and N-vinylpyrrolidone (NVP) (unconjugated vinyl monomer). The tert-butyldimethylsilyl ether and sulfonyl fluoride groups at the α and ω positions of the obtained linear polymer precursors (L-PNIPAAm and L-PVP) are verified by 1 H, 13 C, and 19 F NMR spectra. Subsequent intramolecular SuFEx click cyclization of the α,ω-heterofunctionalized linear precursors in air at room temperature conveniently yields the corresponding cyclic polymers (C-PNIPAAm and C-PVP). Overall, this is the first report on the preparation of cyclic polymers based on the SuFEx reaction under ambient conditions. It is envisioned that the approach may open an avenue for the formation of cyclic polymers.

Protein-resistant properties of poly(N-vinylpyrrolidone)-modified gold surfaces: The advantage of bottle-brushes over linear brushes.

Poly(N-vinylpyrrolidone) (PVP)-modified surfaces have been shown to possess excellent protein resistance and good biocompatibility. However, PVP-modified surfaces with different molecular architectures have not been prepared, and their protein-resistant properties have not been studied. Herein, gold surfaces modified with linear PVP brush and PVP bottle-brush architectures were prepared by photoinitiated surface grafting polymerization. Ellipsometry, X-ray photoelectron spectroscopy (XPS), water contact angle, Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) were utilized to characterize the prepared surfaces. The protein-resistant properties were investigated by a quartz crystal microbalance with dissipation (QCM-D) with bovine serum albumin (BSA), fibrinogen (Fg) and lysozyme (Lyz). Compared with the ungrafted QCM-D chips, the PVP bottle-brush-grafted chips (9.3 nm thickness) showed superior protein resistance over linear PVP brush-grafted chips (9.9 nm thickness). Furthermore, the PVP bottle-brushes reduced the levels of BSA, Fg and Lyz adsorption by 97%, 85% and 69%, respectively. Moreover, to demonstrate potential applications as functional biosensors and in the biomedical field, PVP bottle-brushes containing glycopolymer-grafted gold surfaces were fabricated. Laser scanning confocal microscopy (LSCM) demonstrated that these glycopolymer surfaces showed excellent protein resistance and specific ConA binding ability. Overall, we speculate that the data presented here can provide useful information for the development of excellent antifouling materials and functional biosensors.

Design, Synthesis, and Application of a Difunctional Y-Shaped Surface-Tethered Photoinitiator.

Mixed homopolymer brushes have unique interfacial properties that can be exploited for both fundamental studies and applications in technology. Herein, the synthesis of a new catechol-based biomimetic Y-shaped binary photoinitiator (Y-photoinitiator) and its applications for surface modification with polymer brushes through both "grafting to" and "grafting from" strategies are reported. The "leg" of the Y consists of a catechol group as surface anchoring moiety. The arms are photoinitiator moieties that can be "addressed" independent of each other by radiation of different wavelengths. Using ultraviolet and visible light successively, each arm of the Y-photoinitiator was activated, thereby allowing the synthesis of Y-shaped block copolymer brushes with dissimilar polymer chains. The suitability of the Y-photoinitiator for surface modification was first investigated using N-vinylpyrrolidone and styrene as the model monomers for successive UV-photoiniferter-mediated polymerization and visible-light-induced polymerization, respectively. Switching of the wetting properties of the Y-shaped block copolymer brush poly( N-vinylpyrrolidone)- block-poly(styrene) (PVP- b-PS)-grafted surfaces by contact with different solvents was also investigated. To further exploit this novel Y-photoinitiator for the preparation of functional interfaces, Y-shaped block copolymer brushes poly(1-(2-methacryloyloxyhexyl)-3-methylimidazolium bromide)- block-poly( N-vinylpyrrolidone- co-glycidyl methacrylate) (PIL(Br)- b-P(NVP- co-GMA)) were also prepared and subsequently functionalized with the cell-adhesive arginine-glycine-aspartic acid (RGD) peptides by reaction with the glycidyl groups (PILPNG-RGD). The PILPNG-RGD grafted surfaces showed excellent cell-adhesive, bacteriostatic, and bactericidal properties. Thus, it can be concluded that further exploitation of this novel Y-photoinitiator for graft polymerization should allow the preparation of a wide range of functional interfaces with tailored properties.

A rapid one-step surface functionalization of polyvinyl chloride by combining click sulfur(vi)-fluoride exchange with benzophenone photochemistry.

Polyvinyl chloride (PVC) is an important biomedical material, but there is a lack of convenient functionalization methods. Here, a rapid, effective and simple one-step strategy for PVC surface functionalization by combining the "sulfur(vi)-fluoride exchange" (SuFEx) reaction with benzophenone photochemistry is presented.

"Click-chemical" modification of cellulose acetate nanofibers: a versatile platform for biofunctionalization.

Cellulose acetate nanofibers have attracted considerable interest in the biomedical sciences, but lack convenient biofunctionalization methods. In this work the "sulfur(vi)-fluoride exchange reaction", a new type of click chemistry, is used for the first time to overcome many of the difficulties previously encountered and provide a platform for biofunctionalization generally.

Facile fabrication of a "Catch and Release" cellulose acetate nanofiber interface: a platform for reversible glycoprotein capture and bacterial attachment.

Surfaces engineered to selectively capture and release target biomolecules and cells "on demand" are of considerable interest in a variety of biomedical applications, such as diagnostics and detection. In this work, a strategy is proposed to achieve "catch and release" using boronic acid ligand-functionalized electrospun cellulose acetate (CA) nanofiber mats. To achieve this goal, a simple method based on the one-step visible light-induced grafting copolymerization of 3-(acrylamido)phenylboronic acid (BA) and acrylamide (AM) is established. The copolymer poly(AM-co-BA)-grafted CA nanofiber mats (CA-g-P(AM-co-BA)) showed high capacity for the binding of glycoproteins such as horseradish peroxidase (HRP) and ovalbumin (OVA) under alkaline (pH 9.0) and physiological conditions (pH 7.4). Moreover, the bound glycoproteins can be released from the CA-g-P(AM-co-BA) mats by simple exposure to an acetic acid-sodium acetate (HAc-NaAc) buffer solution (pH 4.0). In addition, this system can be applied to directly extract glycoproteins from egg white samples. Likewise, the CA-g-P(AM-co-BA) mats acted as favorable substrates for Gram-negative E. coli bacterial attachment. The release of the attached bacteria is triggered by competitive sugar binding involving the addition of glucose. It can be envisioned that such boronic acid ligand-functionalized CA nanofiber mats that can "catch and release" biomolecules and bacterial cells hold considerable promise for diverse applications.