Multiresponsive Bilayer Hydrogel Actuator with Switchable Shape Morphing Capability and Visible Color/Fluorescence Change.

Bilayer hydrogels, endowed with multiresponsive and switchable color-changing properties, have garnered significant attention for bioinspired artificial intelligent materials. However, the design and fabrication of such hydrogels that can fully mimic the adaptation of the live organism, i.e., simultaneous changes in shape, fluorescent, and/or visible color, still remain significant challenges. Herein, a multiresponsive (e.g., temperature, salt, and pH) and multiadaptive (shape, fluorescent color, and visible color changes) hydrogel was fabricated by employing monomers featuring pH-responsive fluorescence 4-(2-(4-(dimethylamino) phenyl)-1-isocyanovinyl) phenol (DP) and switchable color-changing 4-(2-sulfethyl) -1-(4-vinylbenzyl) pyridinium betaine (VPES). The bilayer hydrogel comprises a temperature- and pH-responsive gel layer, poly(N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate), along with a pH-, temperature-, and salt-responsive gel layer, poly(acrylamide-co-2-(dimethylamino)ethyl methacrylate-co-VPES)@DP. Due to the opposite swelling/shrinking behavior between the two layers, the prepared hydrogel exhibits shape changes in response to thermal, salt, and pH stimuli, along with switchable fluorescent color and visible color change that originate from DP and polyVPES, respectively. Apart from multiresponsive behavior, this hydrogel also shows an excellent antifatigue property and high sensitivity, which makes it hold significant potential in many applications. We anticipate that this strategy to realize multiresponsive capability in this work can also inspire the design of the biomimetic smart materials.

Weight status changes from childhood to adulthood were associated with cardiometabolic outcomes in adulthood.

AIM: Few studies have assessed the association between weight changes from childhood to adulthood and cardiometabolic factors in adulthood. The aim of this study was to explore the relationships between weight changes from childhood to adulthood and cardiometabolic factors in adulthood using national Chinese data. METHODS: We included 649 participants from the China Health and Nutrition Survey from 1989 to 2009 and divided them into four groups by their body mass index from 6 to 37 years of age. They were selected using multistage random cluster sampling from 15 areas with large variations in economic and social development. Poisson regression models assessed associations between weight status changes and cardiometabolic outcomes in adulthood. RESULTS: The risk of multiple abnormal cardiometabolic outcomes in adulthood was increased in the 126 subjects with normal weight in childhood but overweight or obesity in adulthood and the 28 with obesity at both ages, compared to the 462 with normal weight at both ages. There was insufficient evidence to demonstrate that the 33 who had weight issues as children, but not as adults, had an increased risk. CONCLUSION: Being overweight or obese in both childhood and adulthood or during adulthood only increased the risk of abnormal cardiometabolic outcomes in adulthood. Larger studies need to investigate whether weight problems in childhood, but not adulthood, increase the risk.

In Situ Growth of Functional Hydrogel Coatings by a Reactive Polyurethane for Biomedical Devices.

Surface modification of thermoplastic polyurethane (TPU) could significantly enhance its suitability for biomedical devices and public health products. Nevertheless, customized modification of polyurethane surfaces with robust interfacial bonding and diverse functions via a simple method remains an enormous challenge. Herein, a novel thermoplastic polyurethane with a photoinitiated benzophenone unit (BPTPU) is designed and synthesized, which can directly grow functional hydrogel coating on polyurethane (PU) in situ by initiating polymerization of diverse monomers under ultraviolet irradiation, without the involvement of organic solvent. The resulting coating not only exhibits tissue-like softness, controllable thickness, lubrication, and robust adhesion strength but also provides customized functions (i.e., antifouling, stimuli-responsive, antibacterial, and fluorescence emission) to the original passive polymer substrates. Importantly, BPTPU can be blended with commercial TPU to produce the BPTPU-based tube by an extruder. Only a trace amount of BPTPU can endow the tube with good photoinitiated capacity. As a proof of concept, the hydrophilic hydrogel-coated BPTPU is shown to mitigate foreign body response in vivo and prevent thrombus formation in rat blood circulation without anticoagulants in vitro. This work offers a new strategy to guide the design of functional polyurethane, an elastomer-hydrogel composite, and holds great prospects for clinical translation.

Zwitterionic nanocapsule-based wound dressing with the function of gradient release of multi-drugs for efficient wound healing.

Efficient wound healing has attracted great interest due to the prevalence of skin damage. It is still highly desired yet challenging to construct a multi-drug loaded wound dressing that can release different drugs at different times to meet specific requirements towards different healing stages. Herein, a wound dressing was developed based on thermoresponsive zwitterionic nanocapsules (ZNs) that were sandwiched between two double-layered fabrics to regulate the multiple drug release pathway. The salt-response of the obtained ZNs was greatly suppressed while its transition temperature was regulated to be ∼37 °C to fit the needs of the physiological environment. Two bioactive substances, human basic fibroblast growth factor (bFGF) for tissue regeneration and norfloxacin for anti-inflammation, were loaded in the ZNs and on the surface of fabrics, respectively, to achieve separative gradient release. The in vitro drug release tests revealed that norfloxacin could be released relatively fast (∼24 h) while the release rate of bFGF was much slower (∼168 h), matching the specific time requirements of inflammation and proliferation stages very well. The in vivo wound healing experiment also confirmed the high wound healing efficiency of the wound dressing developed here, compared to the wound dressings without gradient release characteristics. We believe the strategy illustrated here will provide new insights into the design and biomedical applications of zwitterionic nanocapsules.

Polysaccharide-Based Injectable Hydrogels with Fast Gelation and Self-Strengthening Mechanical Kinetics for Oral Tissue Regeneration.

Oral defects lead to a series of function disorders, severely threatening the patients' health. Although injectable hydrogels are widely studied in tissue regeneration, their mechanical performance is usually stationary after implant, without further self-adaption toward the microenvironment. Herein, an injectable hydrogel with programmed mechanical kinetics of instant gelation and gradual self-strengthening along with outstanding biodegradation ability is developed. The fast gelation is realized through rapid Schiff base reaction between biodegradable chitosan and aldehyde-modified sodium hyaluronate, while self-strengthening is achieved via slow reaction between redundant amino groups on chitosan and epoxy-modified hydroxyapatite. The resultant hydrogel also possesses multiple functions including (1) bio-adhesion, (2) self-healing, (3) bactericidal, (4) hemostasis, and (5) X-ray in situ imaging, which can be effectively used for oral jaw repair. We believe that the strategy illustrated here will provide new insights into dynamic mechanical regulation of injectable hydrogels and promote their application in tissue regeneration.

Spontaneous and rapid electro-actuated snapping of constrained polyelectrolyte hydrogels.

Venus flytrap and bladderwort, capable of rapid predation through a snapping transition, have inspired various designs of soft actuators and robots with fast actions. These designs, in contrast to their natural counterparts, often require a direct force or pressurization. Here, we report a bistable domal hydrogel structure capable of spontaneous and reversible snapping under an electric field. Unlike a mechanical force, the electric field does not drive the gel directly. Instead, it redistributes mobile ions that direct the migration of water molecules and bends the polyelectrolyte hydrogel. Subject to constraint from surrounding neutral gel, the elastic energy accumulates until suddenly released by snapping, just like the process in natural organisms. Several proof-of-concept examples, including an optical switch, a speedy catcher, and a pulse pump, are designed to demonstrate the versatile functionalities of this unit capable of articulate motion. This work should bring opportunities to devise soft robotics, biomedical devices, etc.

Photo-switchable supramolecular comb-like polymer brush based on host-guest recognition for use as antimicrobial smart surface.

Bacterial infections from biomedical devices pose a great threat to the health of humans and thus place a heavy burden on society. Therefore, developing efficient antibacterial surfaces has attracted much attention. However, it is a challenge to identify or develop a combination that efficiently integrates multiple functions via topological tailoring and on-demand function-switch via non-contact and noninvasive stimuli. To resolve this issue, a highly hydrophilic comb polymer brush was constructed here based on supramolecular host-guest recognition. Azobenzene (azo)-modified antifouling and antibacterial polymers were incorporated into cyclodextrin (CD)-modified antifouling polymer brushes grafted on the surface. The surface thus obtained possessed excellent antifouling performance with a low bacterial density of ∼6.25 × 105 cells per cm2 after 48 h and exhibited a high efficiency of ∼88.2% for killing bacteria. Besides, irradiation with UV light resulted in the desorption of the azo-polymers and a release of ∼85.1% attached bacteria. Irradiating visible light led to the re-adsorption of azo-polymers, which regenerated the fresh surface; the process could be repeated for at least three cycles, and the surface still maintained low bacterial attachments with a cell density of ∼7.10 × 105 cells per cm2, high sterilization efficiency of ∼93.8%, and a bacteria release rate of ∼83.1% in the 3rd cycle. The photo-switchable antibacterial surface presented in this research will provide new insights into the development of smart biomedical surfaces.

Ionic interaction-driven switchable bactericidal surfaces.

Bacteria in the external environment inevitably invade the wound and subsequently colonize the wound surface during surgery and biomedical operations, which slows down the process of wound healing and tissue repair; this poses a significant threat to human health. Therefore, the development of an intelligent antibacterial surface has become the focus of research in the field of antimicrobial strategies, which has important social and economic significance. Here, we present a simple approach of producing an ionic interaction-driven anionic activation substratum which is then functionalized with cationic molecules through coulombic interactional immobilization. The switchable multifunctional antibacterial surface can decrease bacterial attachment and inactivate the attached microorganisms, thus overcoming the conventional challenge for antibacterial surfaces. Briefly, poly (3-sulfopropyl methacrylate potassium salt) (PSPMA) brushes were constructed by surface-initiated atom transfer radical polymerization on silicon or cotton fabric substrates, and a positive-charged component, namely lysozyme (LYZ), hexadecyl trimethyl ammonium bromide (CTAB) or chitosan (CS), was loaded on negative-charged sulfonate groups through electrostatic interactions. The resultant brush-grafted surfaces exhibited more than ∼95.5% bactericidal efficacy and ∼92.8% release rate after the introduction of an adequate amount of contra-ions (1.0 M; Na+ & Cl-) against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, thus achieving a regenerated surface through the cyclic process of "assembly-dissociation". Smart cotton fabric (Fabric-PSPMA/LYZ and Fabric-PSPMA/CS) surfaces were constructed, which were found to promote wound epidermal tissue regeneration with a higher efficiency after 7-day in vivo studies. This ionic interaction-driven method used in the present work is simple and can reversibly renew antibacterial surfaces, which will help in the wider utilization of switchable antibacterial materials with a more ecologic and economic significance. STATEMENT OF SIGNIFICANCE: Smart antibacterial surfaces with renewable characteristics have attracted considerable interests over the past few years. Here, we used ionic interaction-driven force to manipulate dynamic conformational changes in PSPMA surface brushes, accompanied by highly switchable bacteria killing and bacteria releasing behaviors. Different cationic molecules were also designed for assembly/dissociation on the PSPMA-modified surfaces, and the essential parameters, including chemical structures, molecular weight, and cationic charge density, were investigated. With the refined structural combinations and the balance of bacteria killing/bacteria releasing behaviors, smart cotton fabrics (e.g., Fabric-PSPMA/lysozyme and Fabric-PSPMA/chitosan) were designed that could promote wound healing and tissue repair. These results contribute to the fundamental understanding of a switchable cationic-anionic pair design and the corresponding practical, renewable, highly antibacterial fabric.

Versatile and Simple Strategy for Preparing Bilayer Hydrogels with Janus Characteristics.

Bilayer hydrogels are attracting tremendous attention for their capability to integrate several different functions on the two sides of the gel, that is, imparting the gel with Janus characteristics, which is highly desired in many engineering and biomedical applications including soft actuators, hydrogel patches, and wearable electronics. However, the preparation process of the bilayer materials usually involves several complicated steps and is time-consuming, while the interfacial bonding is another main concern. Here, a simple and versatile method is proposed to obtain bilayer hydrogels within just one step based on the method of introducing viscosity contrast of the precursors for different layers. The bilayer structure can be well maintained during the whole preparation process with a constrained interfacial molecular exchange to ensure the strong bonding strength. The key requirements for forming distinct bilayer structures in situ are studied and discussed in detail. Bilayer hydrogels with different chemical designs are prepared via this strategy to tailor the good distribution of desired functions for soft actuators, wound healing patches, and wearable electronics. We believe that the strategy illustrated here will provide new insights into the preparation and application of bilayer materials.

Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth.

Background: Birth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors. Methods: We included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22-27, 28-36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors. Results: Fetal weight at each period was positively associated with insulin levels, with stronger association at 28-36 weeks (ß, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (ß, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28-36 (ß, -0.32; 95% CI, -0.39 to -0.24) and ≥37 weeks (ß, -0.26; 95% CI, -0.31 to -0.21) was negatively associated with triglyceride levels, whereas weight at 28-36 weeks was positively associated with HDL levels (ß, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22-27 weeks was associated with increased levels of insulin, glucose, and HDL. Conclusions: Fetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.

Zwitterionic Nanocapsules with Salt- and Thermo-Responsiveness for Controlled Encapsulation and Release.

Intelligent polymer nanocapsules that can not only encapsulate substances efficiently but also release them in a controllable manner hold great potential in many applications. To date, although intensive efforts have been made to develop intelligent polymer nanocapsules, how to construct the well-defined core/shell structure with high stability via a straightforward method remains a considerable challenge. In this work, the target novel zwitterionic nanocapsules (ZNCs) with a stable hollow structure were synthesized by inverse reversible addition fragmentation transfer (RAFT) miniemulsion interfacial polymerization. The shell gradually grew from the water/oil interface due to the interfacial polymerization, accompanied by the cross-linking of the polyzwitterionic networks, where the core/shell structure could be well-tuned by adjusting the precursor compositions. The resultant ZNCs exhibited a salt-/thermo-induced swelling behavior through the phase transition of the external zwitterionic polymers. To further investigate the functions of ZNCs, different substances, such as methyl orange and bovine serum albumin (BSA), were encapsulated into the ZNCs with a high encapsulation efficiency of 89.3 and 93.6%, respectively. Interestingly, the loaded substances can be controllably released in aqueous solution triggered by salt or temperature variations, and such responsiveness also can be utilized to bounce off the bacteria adhered on target surfaces. We believe that these designed salt- and thermo-responsive intelligent polymer nanocapsules with well-defined core/shell structures and antifouling surfaces should be a promising platform for biomedical and saline related applications.

Engineering Tough Metallosupramolecular Hydrogel Films with Kirigami Structures for Compliant Soft Electronics.

A simple and effective approach is demonstrated to fabricate tough metallosupramolecular hydrogel films of poly(acrylic acid) by one-pot photopolymerization of the precursor solution in the presence of Zr4+ ions that form coordination complexes with the carboxyl groups and serve as the physical crosslinks of the matrix. Both as-prepared and equilibrated hydrogel films are transparent, tough, and stable over a wide range of temperature, ionic strength, and pH. The thickness of the films can be easily tailored with minimum value of ≈7 µm. Owing to the fast polymerization and gelation process, kirigami structures can be facilely encoded to the gel films by photolithographic polymerization, affording versatile functions such as additional stretchability and better compliance of the planar films to encapsulate objects with sophisticated geometries that are important for the design of soft electronics. By stencil printing of liquid metal on the hydrogel film with a kirigami structure, the integrated soft electronics shows good compliance to cover curved surfaces and high sensitivity to monitor human motions. Furthermore, this strategy is applied to diverse natural and synthetic macromolecules containing carboxyl groups to develop tough hydrogel films, which will open opportunities for the applications of hydrogel films in biomedical and engineering fields.

Cationic peptide-based salt-responsive antibacterial hydrogel dressings for wound healing.

Development of biological dressings has received widespread attentions due to their good breathability, biocompatibility, wettability, and the ability to absorb wound exudate without sticking to the wound. However, current proposed antibacterial hydrogels are limited antibacterial ability, short service life and insufficient biocompatibility, which are still challenging to address intricate practical applications. Here we develop a cationic peptide-based, salt-responsive hydrogel dressing with triple functions of antifouling, bactericidal, and bacterial release by combining ε-poly-l-lysine, poly(ethylene glycol) diglycidyl ether, and poly(DVBAPS-co-GMA) via a one-pot method. These designed hydrogels enabled to further quaternize to enhance antibacterial property due to the presence of amine residues. The resultant hydrogels present good antibacterial activity (>90%), biocompatibility, cell proliferation efficacy (~400%) and adhesiveness. Through in vivo and in vitro antibacterial capability tests, it is also found that hydrogels have good antifouling and sterilization capabilities, and the sterilization rate could reach up to ~96%. In addition, ~94% of the attached bacterial can be released after saline/water switching for several cycles. Taken together, the designed multiple antibacterial dressing prolongs the lifespan relying on reversible salt-responsive release and meet special requirements for wound healing. This work not only provides a platform to highlight its promising potentials in wound management but also gives a custom strategy to biomedical applications.

Programmable Deformations of Biomimetic Composite Hydrogels Embedded with Printed Fibers.

Shape deformations are prevalent in nature, which are closely related to the heterogeneous structures with a feature of fibrous elements embedded in a matrix. The microfibers with specific orientations act as either passive geometrical constraints in an active matrix or active elements in a passive matrix, which generate programmed internal stresses and drive shape morphing under external stimuli. Morphing materials can be designed in a biomimetic way, yet it is challenging to fabricate composite hydrogels with well-distributed fibers by a facile strategy. Here, we demonstrate the fabrication of microfiber-embedded hydrogels facilitated by the extrusion-based printing technology. Programmed deformations are achieved in these hydrogels with microfibers distributed in the upper and/or bottom layers of the gel matrix. Under external stimuli, the microfibers and the gel matrix have different responses that produce internal stresses and result in programmable deformations of the composite gel. Multiple shape transformations are realized in the hydrogel by embedding multiple types of responsive microfibers in the passive or active matrix, which is fabricated with the assistance of multinozzle printing. A soft hook is designed to show the capacity of the composite hydrogel to hold and move an object in a saline solution. This facile and versatile strategy provides an alternative way to prepare biomimetic hydrogels with potential applications in biomedical devices, flexible electronics, and soft robots.

Reversibly Transforming a Highly Swollen Polyelectrolyte Hydrogel to an Extremely Tough One and its Application as a Tubular Grasper.

Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) and its copolymer hydrogels are typical polyelectrolyte gels with extremely high swelling capacity that are widely used in industry. It's common to consider these hydrogels as weak materials that are difficult to toughen. Reported here is a facile strategy to transform swollen and weak poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) [P(AAm-co-AMPS)] hydrogels to tough ones by forming strong sulfonate-Zr4+ metal-coordination complexes. The resultant hydrogels with moderate water content possess high stiffness, strength, and fracture energy, which can be tuned over 3-4 orders of magnitude by controlling the composition and metal-to-ligand ratio. Owing to the dynamic nature of the coordination bonds, these hydrogels show rate- and temperature-dependent mechanical performances, as well as good self-recovery properties. This strategy is universal, as manifested by the drastically improved mechanical properties of hydrogels of various natural and synthetic sulfonate-containing polymers. The toughened hydrogels can be converted to the original swollen ones by breaking up the metal-coordination complexes in alkaline solutions. The reversible brittle-tough transition and concomitant dramatic volume change of polyelectrolyte hydrogels afford diverse applications, as demonstrated by the design of a tubular grasper with holding force a thousand times its own weight for objects with different geometries. It is envisioned that these hydrogels enable versatile applications in the biomedical and engineering fields.

Photodirected Morphing Structures of Nanocomposite Shape Memory Hydrogel with High Stiffness and Toughness.

Shape memory hydrogels have drawn increasing attention in recent years. Practical applications require these hydrogels to have good mechanical properties as well as contactless stimulations to trigger the shape deformations. Here we report a stiff and tough shape memory hydrogel that can transform to various configurations sequentially by phototriggered site-specific deformations. Response of the shape memory hydrogel to near-infrared (NIR) light irradiation was achieved by incorporating gold nanorods (AuNRs) into the glassy gel matrix of poly(methacrylic acid-co-methacrylamide) without compromising the excellent mechanical properties. Owing to the photothermal effect of the AuNRs, the localized temperature rise led to a dramatic decrease in Young's modulus (from 200 to 2 MPa) of the prestretched hydrogel and bending deformation with a programmable direction and amplitude. More complex three-dimensional configurations can be obtained by multidirectional prestretching and shape memorizing the individual parts of the nanocomposite hydrogel. Furthermore, the AuNRs embedded in the gel were aligned along the prestretching direction, leading to anisotropic plasmon resonance. These photomediated programmable deformations of tough shape memory hydrogels should find applications in the biomedical and engineering fields.

Anisotropic nanocomposite films of hydroxypropylcellulose and graphene oxide with multi-responsiveness.

Anisotropic nanocomposite films of hydroxypropylcellulose (HPC) and graphene oxide (GO) were fabricated by blade-coating of the aqueous mixture to align the substance and subsequent solvent evaporation to freeze the oriented structure. Owing to the anisotropic structure, the composite films showed anisotropic mechanical properties and response to external stimuli. The influences of GO content, stretch rate, and relative humidity on the anisotropic structure and mechanical properties of the films were investigated. The incorporation of GO did not destroy the anisotropic structure of the HPC film, but improved the mechanical properties to some extent and favoured the bending deformation and locomotion of the composite film under the humidity gradient. These behaviours were associated with the large aspect ratio and excellent gas barrier property of GO nanosheets that favoured suppressing the slippage of HPC chains and enhanced the differential volume change at the top and bottom surfaces of the film. The composite HPC film with GO or reduced GO also responded to near-infrared light due to the photothermal effect and the variation of HPC matrix at a high temperature. This facile strategy should be applicable to other natural or synthetic polymers to fabricate anisotropic composite films with potential applications as optical devices, sensors, and actuators.

Spin-coating-assisted fabrication of ultrathin physical hydrogel films with high toughness and fast response.

Hydrogel films have promising applications in medical dressings, flexible electronics, etc. However, it is challenging to fabricate ultrathin hydrogel films with high toughness and controllable thickness. Here, we report a facile approach to prepare tough physical hydrogel films by spin-coating of a poly(acrylic acid-co-acrylamide) (P(AAc-co-AAm)) solution and subsequent gelation in FeCl3 solution to form carboxyl-Fe3+ coordination complexes. The thickness of the obtained gel films, ranging from several to hundreds of micrometers, was easily tunable by adjusting the spin conditions and polymer concentration. The thus obtained hydrogel films showed excellent mechanical properties, with tensile breaking strengths of 0.6-14.5 MPa, breaking strains of 140-840%, Young's moduli of 0.1-61.7 MPa, and tearing fracture energies of 300-1300 J m-2. Based on this approach, responsive tough hydrogel films can also be prepared by spin-coating of a poly(acrylic acid-co-N-isopropylacrylamide) (P(AAc-co-NIPAm)) solution. The obtained gel films showed a fast response (<60 s) and a large output force (∼0.2 MPa) triggered by a concentrated saline solution, making them an ideal material in the design of chemomechanical devices. Furthermore, a bilayer hydrogel film was fabricated by two-step spin-coating of P(AAc-co-NIPAm) and P(AAc-co-AAm) solutions, which showed reversible bending deformation under external stimuli. This simple yet effective approach should be applicable to other systems to prepare versatile hydrogel films with tunable thickness and promising applications in diverse areas.