UV Light-Mediated Hydrolytic Reaction to Develop Magnetic Hydrogel Actuators with Spatially Distributed Ferriferous Oxide Microparticles.

Magnetic hydrogel actuators are developed by incorporating magnetic fillers into the hydrogel matrix. Regulating the distribution of these fillers is key to the exhibited functionalities but is still challenging. Here a facile way to spatially synthesize ferrosoferric oxide (Fe3O4) microparticles in situ in a thermal-responsive hydrogel is reported. This method involves the photo-reduction of Fe3+ ions coordinated with carboxylate groups in polymer chains, and the hydrolytic reaction of the reduced Fe2+ ions with residual Fe3+ ions. By controlling the irradiation time and position, the concentration of Fe3O4 microparticles can be spatially controlled, and the resulting Fe3O4 pattern enables the hydrogel to exhibit complex locomotion driven by magnet, temperature, and NIR light. This method is convenient and extendable to other hydrogel systems to realize more complicated magneto-responsive functionalities.

Programmable Thermo-Responsive Actuation of Hydrogels via Light-Guided Surface Growth of Active Layers on Shape Memory Substrates.

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light-initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo-reduction-induced dissociation of Fe3+ -carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo-reduced Fe2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape-programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.

Hydrogen Bonding Enables Polymer Hydrogels with pH-Induced Reversible Dynamic Responsive Behaviors.

Poly(acrylic acid-co-N-vinylcaprolactam) (PAN) hydrogels containing multiple hydrogen bonds can exhibit pH-induced reversible dynamic responsive behaviors. When placing a transparent hydrogel in an acid bath, as hydrogen bonds between comonomer units involving protonated COOH groups are formed faster than water diffusion, a nonequilibrium light-scattering state is formed to turn the hydrogel opaque, while as the swelling equilibrium is reached over time, the hydrogel regains its transparency. Likewise, when the transparent, hydrogen-bonded hydrogel is subsequently immersed in DI water, faster water absorption occurs in where more COOH groups are deprotonated, which also generates a light-scattering state leading to opacity, while the transparency is slowly recovered after equilibrium. Using such two-way dynamic transparency evolution, a PAN-based hydrogel material is prepared to demonstrate a dynamic memory system for information memorizing-forgetting and recalling-forgetting.

Controlling CO2 -Responsive Behaviors of Polymersomes Self-Assembled by Coumarin-Containing Star Polymer via Regulating Its Crosslinking Pattern.

An oligo(ethylene glycol)-based star polymer of N2 -(OEG-C)3 with fluorescent coumarin as hydrophobic end groups and dual tertiary amines as the star center is designed and synthesized. Owing to its amphiphilic nature of N2 -(OEG-C)3 , it will self-assemble into hollow vesicles with coumarin groups dispersed in the hydrophobic membrane and exhibits CO2 -responsive behavior due to the protonation of amine centers with CO2 . More importantly, coumarin moieties can either form non-crosslinking with γ-cyclodextrin via the 2/1 host-guest inclusion, or covalently photodimerized by 365 nm light, offering a tunable crosslinking pattern in the hydrophobic membrane and thus adjusting its CO2 -stimulated reorganization and disassembly behaviors of these vesicles in aqueous solution.

LCST-Type Hyperbranched Poly(oligo(ethylene glycol) with Thermo- and CO2 -Responsive Backbone.

A novel hyperbranched lower critical solution temperature (LCST) polymer with sharp temperature and CO2 -responsive behaviors is presented in this study. The target polymer of hyperbranched poly(oligo(ethylene glycol) (HBPOEG) is constructed using POEG as the backbone and tertiary amines as branch points. Phase transition of HBPOEG in aqueous solution is investigated by heating and cooling the system; the results indicate that HBPOEG in aqueous solution has a concentration-dependent phase transition behavior with excellent repeatability. Moreover, LCST of HBPOEG can be tuned by bubbling CO2 into the solution, as the tertiary amines can be protonated and the solubility of the polymer would increase by bubbling CO2 into the system, leading to an increase of LCST of the polymer. Further bubbling N2 to remove CO2 can reversibly turn back the LCST to its original value. This backbone-based hyperbranched LCST polymer with both CO2 and temperature responsiveness can be applied in application areas like drug delivery, gene transfection, functional coatings, etc.

Amphiphilic Imbalance and Stabilization of Block Copolymer Micelles on-Demand through Combinational Photo-Cleavage and Photo-Crosslinking.

An amphiphilic block copolymer of poly(ethylene oxide)-b-poly((N-methacryloxy phthalimide)-co-(7-(4-vinyl-benzyloxyl)-4-methylcoumarin)) (PEO45 -b-P(MAPI36 -co-VBC4 )) is designed to improve the micellar stability during the photo-triggered release of hydrophobic cargoes. Analysis of absorption and emission spectra, solution transmittance, dynamic light scattering, and transmission electron microscopy supports that polymer micelles of PEO45 -b-P(MAPI36 -co-VBC4 ) upon the combinational irradiation of 365 and 254 nm light can be solubilized through the photolysis of phthalimide esters and simultaneously crosslinked via the partially reversible photo-dimerization of coumarins. The photo-triggered release experiment shows that the leakage of doxorubicin molecules from crosslinked micelles can be predictably regulated by controlling the irradiation time of 365 and 254 nm light.

Fabricating Triple-Sensitive Polymer Nano-Aggregates via an Aqueous Iminoboronate Multicomponent Reaction.

A triple-sensitive polymer of poly(ethylene glycol)-iminoboronate nitrobenzyl ethanediol chelate (PEG-INEC) is efficiently fabricated via the convenient aqueous iminoboronate multi-component reaction (MCR) of methoxypolyethylene glycol amine (mPEG-NH2 ), 2-formylphenylboronic acid (FPBA), and bis(2-nitrophenyl) ethanediol (BNPE, a photo-cleavable nitrobenzyl alcohol derivate). The aqueous MCR synthetic procedure is followed using 1 H NMR and turbidity analysis. It is shown that polymer nano-aggregates of PEG-INEC in aqueous solution can be dissociated through the stimuli responsive reactions of the hydrophobic iminoboronate nitrobenzyl ethanediol chelates (INECs) when exposed to UV light, acid, and H2 O2 , respectively. Furthermore, upon the stimulation of combined triggers, the dissociation of polymer nano-aggregates can be accelerated to different extents, resulting in the synergistic release of encapsulated hydrophobic molecules in water. The proposed facile and general method is quite desirable and of great importance in practical applications like drug and gene delivery.

Amphiphilic Polymer Micellar Disruption Based on Main-Chain Photodegradation.

The amphiphilic block copolymer poly(ethylene oxide)-b-poly(N,N'-dihydroxypyromellitimide-hexamethylene diisocyanate) (PEO-b-PNH) with photocleavable N-O urethanes has been prepared to investigate the photodegradation of the hydrophobic main chain and therefore the disruption of copolymer micelles. Measurements of absorption and emission spectra, optical transmittance, DLS analysis, and TEM observations were applied. It was shown that PEO-b-PNH could self-assemble into flower compound micelles in water. The photodegradation of the hydrophobic polyurethane within the micellar core upon irradiation with 365 nm light could be conveniently controlled by changing the irradiation intensity; furthermore, complete micellar disruption could be achieved when 42% of N-O urethanes were photocleaved. By using DOX as the hydrophobic guest, the drug release profile showed a linear leakage of DOX out of the swelling polymer micelles in the initial stage and thereafter a much more quick exponential decay of DOX precipitation because of the micellar disruption upon further irradiation. The diffusion experiment of the leaked DOX into buffer solution (pH 7.4) showed that the DOX leakage could be prominently accelerated by a very short time of 365 nm irradiation, indicating that the N-O photocleavage can serve as a "turn-on" switch for the release of DOX in aqueous media.

2-Nitrobenzyl Borate Based Photolabile Linker for Breakable Polymer Vesicles.

Fluorescent photolabile groups undergoing convenient synthesis and fast cleavage are being explored because of their increasing utility in both synthetic and biological chemistry. Herein, a model photosensitive poly(ethylene glycol)-lipid of NP-B-PEG with a 2-nitrobenzyl 2-pyridinylmethyl borate hydrophobic tail is synthesized. The (1) H-NMR and absorption spectra analysis of NP-B-PEG upon 365 nm irradiation in water supports a rapid photocleavage of nitrobenzyl borate with the concomitant hydrolysis of 2-pyridinylmethyl borate. It is also shown that the borate tail hydrolyzes slowly in water. Fortunately, when the polymer aqueous solution is loaded with the hydrophobic doxorubicin (DOX), the borate hydrolysis can be much retarded. The phototriggered experiment shows a two-stage DOX release: first, the slow leakage as a result of the photocleavage of 2-nitrobenzyl borate before the vesicle disintegration; second, the quick DOX precipitation from the disintegrated vesicles induced by the speeding up hydrolysis of 2-pyridinylmethyl borate.

Light-Triggered Disruption of PAG-Based Amphiphilic Random Copolymer Micelles.

The amphiphilic random copolymer of P(NVP-co-NHPSS) with photocleavable N-O sulfonate side groups has been prepared to investigate the light-triggered disruption of copolymer micelles. Methods of absorption and emission spectra, solution transmittance, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were applied. It was found that P(NVP-co-NHPSS) could form polymeric nanoaggregates in aqueous solution. And the photocleavage of the N-O bond within copolymer micelles upon 365 nm UV light could be conveniently controlled by changing the irradiation intensity, leading to the disruption of copolymer micelles and the photocontrolled release of Nile red encapsulation. And by encapsulating NaLuF4:Gd/Yb/Tm UCNPs inside copolymer micelles, the response of the photocleavable N-O bond to the 980 nm laser was much weaker than the response to 365 nm light; however, the photocontrolled release of Nile red could still be effectively triggered by the NIR light of the 980 nm laser.

Equilibrating immigration and anthracene-maleimide-based Diels-Alder-trapping of octylmaleimide in mixed photo-cross-linked polymer micelles.

It is possible that the hydrophobic guest within amphiphilic polymer micelles may leak out and be captured by other species before polymer micelles adhere to the desired focus because of the complexity in an actual release procedure, rendering the reduced efficiency of the nanocarrier system. To describe such a scenario, two water-soluble fluorescent amphiphilic random copolymers of PAV and PAA with photo-cross-linkable coumarin and anthracene pendants, respectively, were chosen to investigate the equilibrating immigration and maleimide-anthracene-based Diels-Alder-trapping of hydrophobic octylmaleimide guest from one type of photo-cross-linked polymer micelles of PAV85% to another of PAA66% in aqueous solution using the emission and absorption spectra techniques.

Thermal and Near-Infrared Light-Responsive Hydrogel Actuators with Spatiotemporally Developed Polypyrrole Patterns.

Conjugated polymers are commonly adopted to develop electro- and photoresponsive materials due to their superior electronic conductivity and phototothermal convertibility. However, they are usually homogeneously polymerized within the network, which makes their functionalities challenging to spatiotemporally modulate. In this work, we report a convenient and extensible method to develop polypyrrole patterns in a thermally responsive sodium alginate/poly(N-isopropylacrylamide) hydrogel. The polypyrrole pattern is developed by spatial photoreduction of Fe3+ ions into Fe2+ ions and subsequently initiating oxidation polymerization of pyrrole by the residual Fe3+ ions. During this process, carboxylate groups coordinated with Fe3+ ions are also sacrificed in a gradient manner along the thickness direction, and the resulting concentration gradients of the carboxylate group endow the hydrogel with thermal-responsive actuation. The polymerized polypyrrole also renders the hydrogels' prominent temperature-rising behaviors upon NIR light irradiation. By designing the PPy pattern, hydrogels can exhibit versatile actuating behaviors and execute mechanical works such as lifting objects. This method is convenient and can be extended to develop other conjugated polymers in hydrogel systems for versatile applications.

Fabricating 3D Moisture- and NIR Light-Responsive Actuators by a One-Step Gradient Stress-Relaxation Process.

Polymeric materials that can actuate under the stimulation of environmental signals have attracted considerable attention in fields including artificial muscles, soft robotics, implantable devices, etc. To date, the improvement of shape-changing flexibility is mainly limited by their unchangeable shapes and structural and compositional distributions. In this work, we report a one-step treatment process to convert 2D poly(ethylene oxide)/sodium alginate/tannic acid thin films into 3D-shaped moisture- and NIR light-responsive actuators. Spatial surface wetting of the film leads to the release of residual stress generated in film formation in a gradient manner, which drives the wetted regions to bidirectionally bend. By controlling the position and bending amplitude of the wetted regions, designated 3D shapes can be obtained. Moreover, Fe3+ ions in the aqueous solution used for surface wetting can coordinate with carboxylate groups in sodium alginate chains to form a gradient cross-linking network. This gradient network can not only stabilize the resulting 3D shape but also render the film with moisture-responsive morphing behaviors. Fe3+ ions can also self-assemble with tannic acid molecules to form photothermal aggregates, making the film responsive to NIR light. We further show that films with versatile 3D shapes and different modes of deformation can be fabricated by a one-step treatment process. This strategy is convenient and extendable to develop 3D-shaped polymer actuators with flexible shape-changing behaviors.

Stretching-Induced 2D-to-3D Shape Transformation of an Elastic Composite for Sensitivity-Tailorable Soft Electronics.

The shapes of rubbers and elastomers are challenging to alter, and current methods relying on permanent plasticity and dynamic cross-linking strategies are usually laborious and can inevitably compromise the network elasticity. Here, we report a photoresponsive elastic composite that can be programmed into 3D shapes by first UV light irradiation and then stretching. The composite comprises ethylene propylene rubber as the elastic substrate and photoliquefiable azobenzene small molecules as the responsive filler. Upon UV light irradiation, the liquefication of the filler induces the destruction of the crystalline aggregates near the irradiated surface, and after stretching and subsequent stress release, the irradiated part bends to the irradiated side based on a gradient network orientation mechanism. The position and amplitude of bending deformation can be controlled to realize a 2D-to-3D shape transformation. We further show that the resulting 3D-shaped elastomer can integrate with silver conductive paste to develop soft conductive lines with tailorable strain-sensitive conductivities. This study may open a new door for the development of shape-tailorable elastomers and soft electronics with designable strain-sensitive conductivities.

Light-Guided Growth of Gradient Hydrogels with Programmable Geometries and Thermally Responsive Actuations.

Hydrogel actuators have gained considerable interest and experienced significant advancements in recent years. However, the programming of their actuating behaviors is still challenging. Herein, we report the development and regulation of gradient structures of hydrogels for programmable thermally responsive actuating behaviors. The hydrogel actuators are developed by controlling the photoreduction of Fe3+ ions coordinated with carboxylate groups from the substrates and their limited diffusion into the precursor solutions to act as both initiators and crosslinkers. The developed hydrogels show well-defined external geometries and controllable thicknesses under spatiotemporal control of ultraviolet irradiation. The shapes and the actuation amplitudes of the hydrogel actuators can be independently regulated by controlling the formation and photodissociation of Fe3+-carboxylate coordination in the formed gradient networks. Some interesting applications such as the lifting of an object with a specific shape and directional walking are realized. The proposed method can be extended to other hydrogel actuators with different compositions and stimuli-responsive behaviors.

Photoprogrammable Moisture-Responsive Actuation of a Shape Memory Polymer Film.

Humidity-responsive polymeric actuators have gained considerable interest due to their great potential in the fields including soft robotics, artificial muscles, smart sensors, and actuators. However, most of them can only exhibit invariable shape changes, which severely restricts their further exploration and practical use. Herein, we report that programmable humidity-responsive actuating behaviors can be realized by introducing photoprogrammable hygroscopic patterns into shape memory polymers. Poly(ethylene-co-acrylic acid) is selected as a model polymer and the solvent-processed thin films are soft and elastic, whose external shapes can be programmed by a modified shape memory process. On another aspect, an Fe3+-carboxylate coordinating network formed by surface treatments can be spatially dissociated under UV, resulting in transient hygroscopic gradients as active joints for moisture-driven actuation. Moreover, we show that the shape memory effect can be an effective means to adjust the direction as well as the amplitude of the moisture-driven actuating behavior. The proposed strategy is convenient and can be generally extended to other shape memory polymers to realize programmable moisture-responsive actuating behaviors.

Thermal-Responsive Hydrogel Actuators with Photo-Programmable Shapes and Actuating Trajectories.

Thermal-responsive hydrogel actuators have aroused a wide scope of research interest and have been extensively studied. However, their actuating behaviors are usually monotonous due to their unchangeable shapes and structures. Here, we report thermal-responsive poly(isopropylacrylamide-co-2-(dimethylamino)ethyl methacrylate)/alginate hydrogels with programmable external shapes and internal actuating trajectories. The volume phase transition temperatures of the resulting hydrogels can be tuned in a wide temperature range from 32 to above 50 °C by adjusting the monomer composition. While the formation and photo-dissociation of Fe3+-carboxylate tri-coordinates within the entire hydrogel network enable photo-responsive shape memory property, the insufficient dissociation of the tri-coordinates along the irradiation path gives rise to gradient crosslinking for realizing thermal-responsive actuation. Controlling the evolution of the gradient structure facilitates the regulation of the actuating amplitude. Furthermore, we show that the combination of these two types of shape-changing functionalities leads to more flexible and intricate shape-changing behaviors. One interesting application, a programmable hook with changeable actuating behaviors for lifting different objects with specific shapes, is also demonstrated. The proposed strategy can be extended to other types of actuating hydrogels with more advanced actuating behaviors.

Effects of laparoscopic radical surgery in the treatment of colorectal cancer and correlations of VEGF and TGF-ß1 with prognosis.

OBJECTIVE: To investigate the effects of laparoscopic radical surgery on the treatment of colorectal cancer (CRC) and explore the correlations of vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) with prognosis. METHODS: The clinical data of 210 patients with CRC admitted to the Yantai Zhifu Hospital from February 2015 to February 2018 were analyzed retrospectively. Among them, 110 patients were treated with laparoscopic radical surgery and assigned to the observation group, and the rest 100 patients were treated with routine open surgery and included in the open group. The two groups were compared in terms of operation time (OT), intraoperative blood loss (IBL), postoperative exhaust time (PET), length of hospital stays (LOS) and incidence of complications. Patients were also followed up for 3 years to count their survival rates. Serum expression levels of VEGF and TGF-ß1, detected by enzyme-linked immunosorbent assays (ELISAs), were compared before and after treatment, and their correlations with patients' clinicopathological data and prognosis were analyzed. RESULTS: Compared with the open group, patients in the observation group had longer OT, but lower IBL, PET, LOS, and overall incidence of complications. In the observation group, VEGF and TGF-ß1 expression after treatment was remarkably lower than that before treatment and that in the open group. A 3-year survival rate of 80.0% was observed in the observation group. Univariate analysis showed that serum VEGF and TGF-ß1 expression levels were closely related to Dukes staging and lymph node metastasis (LNM) (P<0.05). The Log-Rank test showed that the survival rate of patients with high VEGF and TGF-ß1 expression was remarkably lower than that of those with low expression (P<0.05). According to Cox model multivariate analysis, Dukes staging, LNM, surgical methods and high VEGF and TGF-ß1 expression were all independent risk factors for the prognosis of CRC patients (P<0.05). CONCLUSION: Laparoscopic radical surgery is effective and safe in treating CRC. VEGF and TGF-ß1 are highly expressed in the serum of CRC patients, and are closely related to the tumor staging, LNM and prognosis of patients, which are of great significance for evaluating the condition and prognosis of CRC patients.

Photo-Dissociable Fe3+-Carboxylate Coordination: A General Approach toward Hydrogels with Shape Programming and Active Morphing Functionalities.

An extendable double network design for hydrogels with programmable external geometries and actuating trajectories is presented. Chemically cross-linked polyacrylamide as the first network penetrated with linear alginate chains is prepared for demonstration. The coordination of Fe3+ ions with carboxylate groups in alginate chains acts as the second network, and its dissociation through photoreduction is utilized to realize the photoresponsive shape memory property; the shape fixity ratio and shape recovery ratio both exceed 90%. The gradient dissociation of Fe3+-carboxylate coordination under UV facilitates 3D programming of hydrogel geometry. On another aspect, the resulted cross-linking gradient differentiates the extent and rate of solvent-induced volume change of the PAAm network, endowing the hydrogel with photo-programmable solvent-driven actuating behavior. Furthermore, by inducing the formation of Fe3+-carboxylate coordination within the entire network for shape programming and cross-linking gradients in specific regions as active joints, hydrogels with designed actuating behaviors based on specific 3D shapes are realized. The shape memory and active morphing functionalities enabled by photo-dissociable Fe3+-carboxylate coordination in PAAm hydrogel can be generally extended to other hydrogels.

Programmable Humidity-Responsive Actuation of Polymer Films Enabled by Combining Shape Memory Property and Surface-Tunable Hygroscopicity.

Most humidity-responsive polymeric actuators can only exhibit shape transformations between a planar shape in the dry state and a bended three-dimensional (3D) shape when exposed to moisture, and it is challenging to design and prepare hygroscopic actuators with programmable actuating behaviors displayed from sophisticated 3D structures. Herein, we demonstrate that the integration of shape memory property and surface treatment enabled hygromorphic responsivity endows a single-component polymer film with programmable moisture-driven actuating behaviors. The solvent-processed polyethylene-co-acrylic acid (EAA) copolymer film is soft and stretchable at room temperature, and has a good thermal-responsive shape memory property. By surface treatment using base/acid solutions, the reversible gradient conversion between carboxyl groups and carboxylate salts along the thickness direction enables the film to exhibit designed hygroscopic actuations. The shape memory property and moisture-driven actuating behaviors can be combined to realize 3D-3D morphing by first programming the films into 3D shapes and then conducting the surface treatments. Both shape programming and surface treatment processes can be reprogrammed to make the actuation behavior readily tunable. We also show that the created surface patterns can act as moisture-sensitive conducting paths to detect human breathes, and the combination of shape memory, moisture-responsive morphing and conductivity change leads to some interesting applications such as smart switch in conducting circuit. This work provides a new and general strategy for the design of advanced humidity-responsive actuators.