Recent Developments in Functional Polymers via the Kabachnik-Fields Reaction: The State of the Art.

Recently, multicomponent reactions (MCRs) have attracted much attention in polymer synthesis. As one of the most well-known MCRs, the Kabachnik-Fields (KF) reaction has been widely used in the development of new functional polymers. The KF reaction can efficiently introduce functional groups into polymer structures; thus, polymers prepared via the KF reaction have unique α-aminophosphonates and show important bioactivity, metal chelating abilities, and flame-retardant properties. In this mini-review, we mainly summarize the latest advances in the KF reaction to synthesize functional polymers for the preparation of heavy metal adsorbents, multifunctional hydrogels, flame retardants, and bioimaging probes. We also discuss some emerging applications of functional polymers prepared by means of the KF reaction. Finally, we put forward our perspectives on the further development of the KF reaction in polymer chemistry.

A Photoorganizable Triple Shape Memory Polymer for Deployable Devices.

Inspired by the action and healing process from living organisms, developing deployable devices using stimuli-responsive materials, or "smart" deployable devices, is desired to realize remote-controlled programmable deformation with additional in situ repair to perform multiple tasks while extending their service life in aerospace. In this work, a photoorganizable triple shape memory polymer (POTSMP) is reported, which is composed of an azobenzene-containing thermoplastic polyurethane. Upon UV and visible illumination, this POTSMP performs arbitrary programming of two temporary shapes and precise and stepwise shape recovery, exhibiting various temporary shapes adapted to different aerospace applications. On the other hand, rapid light-reconfiguration in seconds, including light-reshaping and light-welding, is achieved in response to UV irradiation, allowing in situ localized process and repair of permanent shape. Combining these photoorganizable operations, deformable devices with complex 2D/3D structures are facilely manufactured with no need of special molds. It is envisioned that this POTSMP can expand the potential of photoresponsive TSMPs in smart deployable devices.

Stimuli-Responsive Multifunctional Phenylboronic Acid Polymers Via Multicomponent Reactions: From Synthesis to Application.

Stimuli-responsive polymers undergo changes under different environmental conditions. Among them, phenylboronic acid (PBA) containing polymers (PBA-polymers) are unique, because they can selectively react with diols to generate borates that are sensitive to pH, sugars, and H2 O2 , and can be effectively used to synthesize smart drug carriers and self-healing hydrogels. Recently, multifunctional PBA-polymers (MF-PBA-polymers) have been developed using multicomponent reactions (MCRs) to introduce PBA groups into polymer structures. These MF-PBA-polymers have features similar to those of traditional PBA-polymers; moreover, they exhibit additional properties, such as fluorescence, antimicrobial activity, and antioxidant capability, when different MCRs are used. In this mini review, the preparation of these MF-PBA-polymers are summarized and the new properties/functions that have been introduced into these polymers using different MCRs are discussed. The uses of these MF-PBA-polymers as fluorescent cell anticoagulants, drug carriers, and gelators of functional self-healing hydrogels have been discussed. Additionally, the challenges encountered during their preparation are discussed and also the future developments in this field are touched upon.

Dynamic Interfacial Regulation by Photodeformable Azobenzene-Containing Liquid Crystal Polymer Micro/Nanostructures.

Photoresponsive materials offer local, temporal, and remote control over their chemical or physical properties under external stimuli, giving new tools for interfacial regulation. Among all, photodeformable azobenzene-containing liquid crystal polymers (azo-LCPs) have received increasing attention because they can be processed into various micro/nanostructures and have the potential to reversibly tune the interfacial properties through chemical and/or morphological variation by light, providing effective dynamic interface regulation. In this feature article, we highlight the milestones in the dynamic regulation of different interfacial properties through micro/nanostructures made of photodeformable azobenzene-containing liquid crystal polymers (azo-LCPs). We describe the preparation of different azo-LCP micro/nanostructures from the aspects of materials and processing techniques and reveal the importance of mesogen orientation toward dynamic interfacial regulation. By introducing our recently developed linear azo-LCP (azo-LLCP) with good mechanical and photoresponsive performances, we discuss the challenge and opportunity with respect to the dynamic light regulation of two- and three-dimensional (2D/3D) micro/nanostructures to tune their related interfacial properties. We have also given our expectation toward exploring photodeformable micro/nanostructures for advanced applications such as in microfluidics, biosensors, and nanotherapeutics.

Light-Directed Liquid Manipulation in Flexible Bilayer Microtubes.

Flexible microfluidic systems have potential in wearable and implantable medical applications. Directional liquid transportation in these systems typically requires mechanical pumps, gas tanks, and magnetic actuators. Herein, an alternative strategy is presented for light-directed liquid manipulation in flexible bilayer microtubes, which are composed of a commercially available supporting layer and the photodeformable layer of a newly designed azobenzene-containing linear liquid crystal copolymer. Upon moderate visible light irradiation, various liquid slugs confined in the flexible microtubes are driven in the preset direction over a long distance due to photodeformation-induced asymmetric capillary forces. Several light-driven prototypes of parallel array, closed-loop channel, and multiple micropump are established by the flexible bilayer microtubes to achieve liquid manipulation. Furthermore, an example of a wearable device attached to a finger for light-directed liquid motion is demonstrated in different gestures. These unique photocontrollable flexible microtubes offer a novel concept of wearable microfluidics.

Hydrolyzable Poly[Poly(Ethylene Glycol) Methyl Ether Acrylate]-Colistin Prodrugs through Copper-Mediated Photoinduced Living Radical Polymerization.

Through the recently developed copper-mediated photoinduced living radical polymerization (CP-LRP), a novel and well-defined polymeric prodrug of the antimicrobial lipopeptide colistin has been developed. A colistin initiator (Boc5-col-Br2) was synthesized through the modification of colistin on both of its threonine residues using a cleavable initiator linker, 2-(2-bromo-2-methylpropanoyloxy) acetic acid (BMPAA), and used for the polymerization of acrylates via CP-LRP. Polymerization proceeds from both sites of the colistin initiator, and through the polymerization of poly(ethylene glycol) methyl ether acrylate (PEGA480), three water-soluble polymer-colistin conjugates (col-PPEGA, having degrees of polymerization of 5, 10, and 20) were achieved with high yield (conversion of ≥93%) and narrow dispersities (D < 1.3) in 2-4 h. Little or no effect on the structure and activity of the colistin was observed during the synthesis, and most of the active colistin can be recovered from the conjugates in vitro within 2 days. Furthermore, in vitro biological analyses including disk diffusion, broth microdilution, and time-kill studies suggested that all of the conjugates have the ability to inhibit the growth of multidrug-resistant (MDR) Gram-negative bacteria, of which col-PPEGA DP5 and DP10 showed similar or better antibacterial performance compared to the clinically relevant colistin prodrug CMS, indicating their potential as an alternative antimicrobial therapy. Moreover, considering the control over the polymerization, the CP-LRP technique has the potential to provide an alternative platform for the development of polymer bioconjugates.

Well-Defined Protein/Peptide-Polymer Conjugates by Aqueous Cu-LRP: Synthesis and Controlled Self-Assembly.

The synthesis of well-defined protein/peptide-polymer conjugates with interesting self-assembly behavior via single electron transfer living radical polymerization in water is described. A range of protein/peptides with different physical and chemical properties have been modified to macroinitiators and optimized polymerization conditions ensure successful polymerization from soluble, insoluble, and dispersed protein/peptide molecules or protein aggregates. This powerful strategy tolerates a range of functional monomers and mediates efficient homo or block copolymerization to generate hydrophilic polymers with controlled molecular weight (MW) and narrow MW distribution. The polymerizations from bovine insulin macroinitiators follow surface-initiated "grafting from" polymerization mechanism and may involve a series of self-assembly and disassembly processes. Synthesized insulin-polymer conjugates form spheres in water, and the self-assembly behavior could be controlled via thermal control, carbohydrate-protein interaction, and protein denaturation.

Dynamic Hydrogels against Infections: From Design to Applications.

Human defense against infection remains a global topic. In addition to developing novel anti-infection drugs, therapeutic drug delivery strategies are also crucial to achieving a higher efficacy and lower toxicity of these drugs for treatment. The application of hydrogels has been proven to be an effective localized drug delivery approach to treating infections without generating significant systemic adverse effects. The recent emerging dynamic hydrogels further show power as injectable formulations, giving new tools for clinical treatments. In this review, we delve into the potential applications of dynamic hydrogels in antibacterial and antiviral treatments and elaborate on their molecular designs and practical implementations. By outlining the chemical designs underlying these hydrogels, we discuss how the choice of dynamic chemical bonds affects their stimulus responsiveness, self-healing capabilities, and mechanical properties. Afterwards, we focus on how to endow dynamic hydrogels with anti-infection properties. By comparing different drug-loading methods, we highlight the advantages of dynamic chemical bonds in achieving sustained and controlled drug release. Moreover, we also include the design principles and uses of hydrogels that possess inherent anti-infective properties. Furthermore, we explore the design principles and applications of hydrogels with inherent anti-infective properties. Finally, we briefly summarize the current challenges faced by dynamic hydrogels and present a forward-looking vision for their future development. Through this review, we expect to draw more attention to these therapeutic strategies among scientists working with chemistry, materials, as well as pharmaceutics.

Chitosan-Based Self-Healing Hydrogel: From Fabrication to Biomedical Application.

Biocompatible self-healing hydrogels are new-generation smart soft materials that hold great promise in biomedical fields. Chitosan-based self-healing hydrogels, mainly prepared via dynamic imine bonds, have attracted broad attention due to their mild preparation conditions, excellent biocompatibility, and self-recovery ability under a physiological environment. In this review, we present a comprehensive overview of the design and fabrication of chitosan-based self-healing hydrogels, and summarize their biomedical applications in tissue regeneration, customized drug delivery, smart biosensors, and three/four dimensional (3D/4D) printing. Finally, we will discuss the challenges and future perspectives for the development of chitosan-based self-healing hydrogels in the biomedical field.

An Integrated Droplet Manipulation Platform with Photodeformable Microfluidic Channels.

Manipulating droplets by light in microscale allows precise control of microfluidics, liquid delivery, micromachines, and so on. Among these applications, microfluidic technology is of particular interest for miniaturization of the portable analysis systems, which require the integration of various liquid operations in one device. Here, a photodeformable microfluidic platform is constructed by combining Laplace pressure and capillary condensation to integrate the transportation, fusion, separation, and mixing of liquid slugs in one chip. The Laplace pressure, attributed to the photodeformation of the liquid crystal polymers, is generated to propel the slug. The capillary condensation is introduced by the delicate design of the fluid channels, allowing the fusion and separation of slugs without any connected microvalves. Catalytic oxidation reaction and protein detection processes are realized in the platform, which are amenable to a variety of miniaturized bio-medical applications, such as portable analysis and point of care testing.

Transparent, High Glass-Transition Temperature, Shape Memory Hybrid Polyimides Based on Polyhedral Oligomeric Silsesquioxane.

Optically transparent polyimides with excellent thermal stability and shape memory effect have potential applications in optoelectronic devices and aerospace industries. A series of optically transparent shape memory polyimide hybrid films are synthesized from 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride (6FDA) and 2,2'-bis-(trifluoromethyl)biphenyl-4,4'-diamine (TFMB) with various polyhedral oligomeric silsesquioxane (POSS) contents and then subjected to thermal imidization. The hybrid films show good optical transparency (>80% at 400 nm and >95% at 500 nm) with cutoff wavelengths ranging from 318 to 336 nm. Following the incorporation of the inorganic POSS structure, the hybrid films exhibit excellent thermal stability with glass transition temperature (Tg) ranging from 351 to 372 °C. The hybrid films possess the highest Tg compared with the previously-reported shape memory polymers. These findings show that POSS is successfully utilized to develop transparent polyimides with excellent thermal stability and shape memory effect.

Photodeformable Azobenzene-Containing Liquid Crystal Polymers and Soft Actuators.

Photodeformable liquid crystal polymers (LCPs) that adapt their shapes in response to light have aroused a dramatic growth of interest in the past decades, since light as a stimulus enables the remote control and diverse deformations of materials. This review focuses on the growing research on photodeformable LCPs, including their basic actuation mechanisms, the various deformation modes, the newly designed molecular structures, and the improvement of processing techniques. Special attention is devoted to the novel molecular structures of LCPs, which allow for easy processing and alignment. The soft actuators with various deformation modes such as bending, twisting, and rolling in response to light are also covered with the emphasis on their photo-induced bionic functions. Potential applications in energy harvesting, self-cleaning surfaces, sensors, and photo-controlled microfluidics are further illustrated. The existing challenges and future directions are discussed at the end of this review.

Rapid, Localized, and Athermal Shape Memory Performance Triggered by Photoswitchable Glass Transition Temperature.

Shape memory polymers that undergo shape recovery at room temperature (RT) are desirable for their potential in vivo applications, yet challenging. Herein, light-triggered athermal shape memory effect of azopolymer networks is reported by photoswitching the glass transition temperature (Tg) rather than external heating. Thanks to the switchable Tg of azopolymer induced by reversible trans-cis isomerization, the entropic energy is trapped in low Tg state (cis-form Tg < RT) to deform into a temporary shape and fixed in high Tg state (trans-form Tg > RT). Upon exposure to UV light, the reduced low Tg allows release of the entropic energy, realizing athermal shape recovery of the permanent shape. By exploring the shape memory performance, we demonstrate diverse light-induced rapid shape recovery from temporary shape to original shape. Because of the instant, precise, and spatiotemporal manipulation of light, programmable shape recovery of surface topography is further extended. We anticipate that this strategy will provide tremendous opportunities for future precise medicine devices and soft robotics.

A Hydrogel-Based Localized Release of Colistin for Antimicrobial Treatment of Burn Wound Infection.

There is an urgent unmet medical need for new treatments for wound and burn infections caused by multidrug-resistant Gram-negative "superbugs," especially the problematic Pseudomonas aeruginosa. In this work, the incorporation of colistin, a potent lipopeptide into a self-healable hydrogel (via dynamic imine bond formation) following the chemical reaction between the amine groups present in glycol chitosan and an aldehyde-modified poly(ethylene glycol), is reported. The storage module (G') of the colistin-loaded hydrogel ranges from 1.3 to 5.3 kPa by varying the amount of the cross-linker and colistin loading providing different options for topical wound healing. The majority of the colistin is released from the hydrogel within 24 h and remains active as demonstrated by both antibacterial in vitro disk diffusion and time-kill assays. Moreover and pleasingly, the colistin-loaded hydrogel performs almost equally well as native colistin against both the colistin-sensitive and also colistin-resistant P. aeruginosa strain in the in vivo animal "burn" infection model despite exhibiting a slower killing profile in vitro. Based on this antibiotic performance along with the biodegradability of the product, it is believed the colistin-loaded hydrogel to be a potential localized wound-healing formulation to treat burn wounds against microbial infection.

A traceless reversible polymeric colistin prodrug to combat multidrug-resistant (MDR) gram-negative bacteria.

Colistin methanesulfonate (CMS) is the only prodrug of colistin available for clinical use for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Owing to its slow and variable release, an alternative is urgently required to improve effectiveness. Herein we describe a PEGylated colistin prodrug whereby the PEG is attached via a cleavable linker (col-aaPEG) introducing an acetic acid terminated poly (ethylene glycol) methyl ether (aaPEG) onto the Thr residue of colistin. Due to the labile ester containing link, this prodrug is converted back into active colistin in vitro within 24h. Compared to CMS, it showed a similar or better antimicrobial performance against two MDR isolates of Pseudomonas aeruginosa and Acinetobacter baumannii through in vitro disk diffusion, broth dilution and time-kill studies. In a mouse infection model, col-aaPEG displayed acceptable bacterial killing against P. aeruginosa ATCC 27853 and no nephrotoxicity was found after systemic administration, suggesting it to be a potential alternative for CMS.

Carbon-dots derived from nanodiamond: photoluminescence tunable nanoparticles for cell imaging.

Water dispersible carbon-dots (CDs) with tunable photoluminescence were synthesized via one-pot hydrothermal oxidation of nanodiamond and subsequently utilized for cell imaging applications. The CDs were characterized by the following techniques including transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, UV-Visible spectroscopy, and fluorescent spectroscopy. Results showed that the size of CDs is mainly distributed at 3-7 nm. Many functional groups were introduced on the surface of CDs during hydrothermal oxidation procedure. Cell morphology observation and cell viability measurement demonstrated the good biocompatibility of CDs, suggesting their potential bioimaging applications.

Nonionic polymer cross-linked chitosan hydrogel: preparation and bioevaluation.

A straightforward method to prepare nonionic polymer (polyacrylamide, PAM) cross-linked chitosan hydrogel has been developed. The chitosan-polyacrylamide (CS-PAM) hydrogel could be quickly obtained by simply mixing of chitosan and polyacrylamide solutions under very benign condition (room temperature, <30 s). The cytotoxicity and hemocompatibility of the CS-PAM hydrogel were subsequently investigated. Cells retained normal morphology even when the concentration of CS-PAM hydrogel in culture system was as high as 640 µg mL(-1), indicating the CS-PAM hydrogel has minimal cytotoxicity to A549 and HeLa cells. Meanwhile, no hemolysis was observed after incubating the CS-PAM hydrogel with red blood cells for 6 h, further suggesting excellent biocompatibility of the hydrogel. Scanning electron microscopy images illustrated that the CS-PAM hydrogel can absorb red blood cells through the interaction between the protonated amine groups on chitosan and the negative charged residues on red blood cell membranes. Given its low cost, simple preparation, and excellent biocompatibility, this CS-PAM hydrogel might be a potential biomaterial for future healthcare and biomedical applications.