Controllable Fabrication of Highly Uniform Sub-10 nm Nanoparticles from Spontaneous Confined Nanoemulsification.

Sub-10 nm nanoparticles are known to exhibit extraordinary size-dependent properties for wide applications. Many approaches have been developed for synthesizing sub-10 nm inorganic nanoparticles, but the fabrication of sub-10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub-10 nm nanodroplets for template synthesis of sub-10 nm polymeric nanoparticles is proposed. This strategy introduces a high-concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular-level impact on interfacial instability for creating sub-10 nm nanoemulsions via self-burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub-10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand-new opportunities to easily create sub-10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.

Thermochromic Photonic Crystal Microspheres with Uniform Color Display and Wide Coloration Range.

Thermochromic microspheres based on poly(N-isopropylacrylamide) attract much attention in detection and sensor due to the noticeable color response and fast response rate. However, some issues such as uneven color display and narrow coloration range still limit their practical applications. Herein, novel thermochromic microspheres with homogeneous color displays and wide thermochromic range are designed by combining the microfluidic technology with the magnetically-induced self-assembly technique and copolymerizing acrylamide (AM) with N-isopropylacrylamide. The photonic crystal structure with especially even colors is fast and conveniently constructed by magnetic assembly. The addition of AM makes the microspheres more hydrophilic and thus leading to a broader coloration range. The relationship between the structural color display and both the microstructures of photonic crystals and the thermo-responsive properties of gel matrix are elucidated. The detectable temperature of microspheres rises to as high as 60°C, and displays bright iridescent color variations from orange to blue-violet in the heating process. Importantly, their shrinking or swelling equilibrium can be reached in 80 and 105 s. Such microspheres are successfully used to visually indicate the appropriate temperature of enzymatic reaction, and have great potential in practical applications such as visual temperature detection and efficiency monitoring of chemical reactions.

Pseudo Polyampholytes with Sensitively Ion-Responsive Conformational Transition Based on Positively Charged Host-Guest Complexes.

Biological polyampholytes are ubiquitous in living organisms with primary functions including serving as transporters for moving chemical molecular species across the cell membranes. Synthetic amphoteric macromolecules that can change their phase states depending on the environment to simulate some properties of natural polyampholytes are of great interest. Here, the implementation of synthetic pseudo polymeric ampholytes is explored with ion-recognition-triggered conformational change. The phase transition behaviors of the ion-recognition-creative polyampholytes that contain deprotonated carboxylic acid groups as negative charges and 18-crown-6 units for forming positively charged host-guest complexes are systematically investigated. The ion-recognition-triggered phase transition behaviors of pseudo polyampholytes significantly depend on cation species and concentrations. Only those specific ions such as K+ , Ba2+ , Sr2+ and Pb2+ ions that can form 1:1 host-guest complexes with 18-crown-6 units in polymers enable control over conformational change like that of traditional pH-dependent polyampholytes. By regulating the content of carboxylic acid groups to match the content of ion-recognized positive charges provided by the host-guest complexes, the pseudo polyampholytes are more sensitive to the recognizable cations. Such ion-recognition-triggered amphoteric characteristics make the pseudo polyampholytes act like biological proteins, nucleic acids, and enzymes as molecular transporters, genetic code storage, and biocatalysts in artificial systems.

Magnetically Assembled Photonic Crystal Gels with Wide Thermochromic Range and High Sensitivity.

Thermochromic poly(N-isopropyl acrylamide) (PNIPAM) photonic crystal gels based on 1D magnetically assembling colloidal nanocrystal clusters have attracted much attention due to its convenient preparation process, striking color response, and good mechanical strength. However, there remain challenges to broaden the thermochromic range and improve the sensitivity for their iridescent color display. Here, a PNIPAM photonic gel with wide thermochromic range and high sensitivity is prepared by using four-arm star poly(ethylene glycol) acrylamide (PEGAAm) as cross-linker at appropriately reduced magnetic field strength as well as cross-linker content. PEGAAm improves the homogeneity of the microstructure in PNIPAM photonic gel and thus maintains the structure colors at a wide temperature range from room temperature to 44 °C. The reduced magnetic field strength of 70 Gs and low cross-linker content (the molar ratio of monomer to cross-linker of 300:1) lead to a large initial lattice spacing of the photonic gel and thus wide diffraction wavelength migration of 194 nm. This optimized PNIPAM gel exhibits vivid iridescent colors from orange-red to indigo blue as temperature increases from 20 to 44 °C with satisfactory repeatability. Therefore, it may be an ideal candidate for temperature sensors and displays with utility and accuracy such as low-temperature burns.

Ultrasensitive microchip based on smart microgel for real-time online detection of trace threat analytes.

Real-time online detection of trace threat analytes is critical for global sustainability, whereas the key challenge is how to efficiently convert and amplify analyte signals into simple readouts. Here we report an ultrasensitive microfluidic platform incorporated with smart microgel for real-time online detection of trace threat analytes. The microgel can swell responding to specific stimulus in flowing solution, resulting in efficient conversion of the stimulus signal into significantly amplified signal of flow-rate change; thus highly sensitive, fast, and selective detection can be achieved. We demonstrate this by incorporating ion-recognizable microgel for detecting trace Pb(2+), and connecting our platform with pipelines of tap water and wastewater for real-time online Pb(2+) detection to achieve timely pollution warning and terminating. This work provides a generalizable platform for incorporating myriad stimuli-responsive microgels to achieve ever-better performance for real-time online detection of various trace threat molecules, and may expand the scope of applications of detection techniques.

[Applications of marine-derived chitosan and alginates in biomedicine].

Marine-derived biopolymers are excellent raw materials for biomedical products due to their abundant resources, good biocompatibility, low cost and other unique functions. Marine-derived biomaterials become a major branch of biomedical industry and possess promising development prospects since the industry is in line with the trend of "green industry and low-carbon economy". Chitosan and alginates are the most commonly commercialized marine-derived biomaterials and have exhibited great potential in biomedical applications such as wound dressing, dental materials, antibacterial treatment, drug delivery and tissue engineering. This review focuses on the properties and applications of chitosan and alginates in biomedicine.

Acyclic Janus-AT Nucleoside Host Channels Precisely Lock Water into Single-File Wires with Local Rotational Flexibility.

Confining polar water molecules to particular geometries demands sophisticated intermolecular interactions, and not many small synthetic molecules have accomplished such a task. Herein, regioisomeric acyclic Janus-AT nucleosides (1 and 2), with a self-complementary fused genetic alphabet and conformationally flexible side chains, have been selectively synthesized. 1 and 2 adopt disparate base-pair motifs from the π-π stacked hydrophobic base moieties and distinct hydrogen bond (HB) interconnections from the hydrophilic sugar residues, which in turn lead to divergent, intricate intermolecular interaction networks with different capacities to confine water molecules. Under the precise control of the host framework of the N8 -regioisomer, separate ordered single-file water wires can be locked through special three-HB clamps into unique inter- and intra-wire geometrical alignments. Localized dynamic synchronized rotations within the fixed framework coordinated by both the host hydroxy groups and guest water molecules were observed in a temperature-induced reversible single-crystal-to-single-crystal transition (SCSCT).

A Novel Thermoresponsive Catalytic Membrane with Multiscale Pores Prepared via Vapor-Induced Phase Separation.

A novel thermoresponsive catalytic polyethersulfone membrane with multiscale pores is developed by constructing silver nanoparticles (Ag NPs) loaded poly(N-isopropylacrylamide) (PNIPAM) nanogels on pore walls of cellular pores as thermoresponsive gates and catalysts via vapor-induced phase separation. The Ag NPs are stably immobilized on the PNIPAM nanogels by an in situ reduction method based on the versatile adhesion and reduction properties of polydopamine. The micrometer cellular pores decorated with Ag NPs loaded PNIPAM nanogels are formed throughout the membrane and act as numerous microreactors with a large pore surface. The proposed membrane exhibits both satisfactory thermoresponsive characteristics and stable catalytic properties. The effects of operation temperature and reactant concentration of feed solution on the catalytic properties are investigated systematically. The results show that the apparent kinetic rate constant of catalytic reduction of 4-nitrophenol (4-NP) in water by reductant sodium borohydride (NaBH4 ), is ranging from 3.7 to 37.9 min-1 at temperatures from 20 to 45 ºC and the molar ratio of NaBH4 to 4-NP from 100:1 to 500:1. When the reactant concentration in feed solution fluctuates, the permeability or throughput of the membrane is simply adjusted by virtue of the thermoresponsive characteristics of membranes to achieve high catalytic conversion of reactant.

A Simple Device Based on Smart Hollow Microgels for Facile Detection of Trace Lead(II) Ions.

A simple device, which is equipped with a non-woven fabric filter medium immobilized with ion-recognizable smart hollow microgels, is developed for facile detection of trace lead(II) ions (Pb2+ ). The ion-recognizable smart microgels are made of poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB), in which the 18-crown-6 groups act as the sensors of Pb2+ and the N-isopropylacrylamide groups act as the actuators. The PNB hollow microgels can isothermally change from a shrunk state to a swollen state in response to recognizing Pb2+ in the aqueous environment due to the electrostatic repulsion among the charged 18-crown-6/Pb2+ complex groups and the enhancement of hydrophilicity of the microgels. Due to the hollow structures, the PNB microgels show remarkable isothermal swelling ratio. Thus, the flux of solution pass through the non-woven fabric filter medium decreases significantly because of the remarkable reduction in the space for liquid flowing upon recognizing Pb2+ . The Pb2+ concentration can be detected quantitatively by simply and easily measuring the change of solution flux using the proposed device, which is operated without external power supply or spectroscopic measurements. The strategy proposed in this study provides a promising method for facile detection of trace Pb2+ in aqueous environments.

Controllable Microfluidic Fabrication of Microstructured Materials from Nonspherical Particles to Helices.

This work reports on a facile and flexible strategy based on the deformation of encapsulated droplets in fiber-like polymeric matrices for template synthesis of controllable microstructured materials from nonspherical microparticles to complex 3D helices. Monodisperse droplets generated from microfluidics are encapsulated into crosslinked polymeric networks via an interfacial crosslinking reaction in microchannel to in situ produce the droplet-containing, fiber-like matrices. By stretching and twining the dried fiber-like matrices, the encapsulated droplets can be flexibly engineered into versatile shapes for template synthesis of controllable nonspherical microparticles and helices. Moreover, magnetic helices can be fabricated by simply dispersing magnetic Fe3 O4 nanoparticles in the droplets to achieve rotational and translational motion under a rotated magnetic field. This work provides a simple and versatile strategy for the template synthesis of advanced functional microstructured materials with flexible shapes.

Stimuli-responsive smart gating membranes.

Membranes are playing paramount roles in the sustainable development of myriad fields such as energy, environmental and resource management, and human health. However, the unalterable pore size and surface properties of traditional porous membranes restrict their efficient applications. The performances of traditional membranes will be weakened upon unavoidable membrane fouling, and they cannot be applied to cases where self-regulated permeability and selectivity are required. Inspired by natural cell membranes with stimuli-responsive channels, artificial stimuli-responsive smart gating membranes are developed by chemically/physically incorporating stimuli-responsive materials as functional gates into traditional porous membranes, to provide advanced functions and enhanced performances for breaking the bottlenecks of traditional membrane technologies. Smart gating membranes, integrating the advantages of traditional porous membrane substrates and smart functional gates, can self-regulate their permeability and selectivity via the flexible adjustment of pore sizes and surface properties based on the "open/close" switch of the smart gates in response to environmental stimuli. This tutorial review summarizes the recent developments in stimuli-responsive smart gating membranes, including the design strategies and the fabrication strategies that are based on the introduction of the stimuli-responsive gates after or during membrane formation, and the positively and negatively responsive gating models of versatile stimuli-responsive smart gating membranes, as well as the advanced applications of smart gating membranes for regulating substance concentration in reactors, controlling the release rate of drugs, separating active molecules based on size or affinity, and the self-cleaning of membrane surfaces. With self-regulated membrane performances, smart gating membranes show great power for use in global sustainable development.

Monodisperse and fast-responsive poly(N-isopropylacrylamide) microgels with open-celled porous structure.

A simple and efficient method is developed to fabricate monodisperse and fast-responsive poly(N-isopropylacrylamide) (PNIPAM) microgels with open-celled porous structure. First, numerous fine oil droplets are fabricated by homogeneous emulsification method and are then evenly dispersed inside monodisperse PNIPAM microgels as porogens via the combination of microfluidic emulsification and UV-initiated polymerization methods. Subsequently, the embedded fine oil droplets inside the PNIPAM microgels are squeezed out upon stimuli-induced rapid volume shrinkage of the microgels; as a result, a spongelike open-celled porous structure is formed inside the PNIPAM microgels. The open-celled porous structure provides numerous interconnected free channels for the water transferring convectively inward or outward during the volume phase transition process of PNIPAM microgels; therefore, the response rates of the PNIPAM microgels with open-celled porous structure are much faster than that of the normal ones in both thermo-responsive shrinking and swelling processes. Because of the fast-responsive characteristics, the microgels with open-celled porous structure will provide ever better performances in their myriad applications, such as microsensors, microactuators, microvalves, and so on.

Competitive molecular-/ion-recognition responsive characteristics of poly(N-isopropylacrylamide-co-benzo-12-crown-4-acrylamide) copolymers with benzo-12-crown-4 as both guest and host units.

Novel dual molecular- and ion-recognition responsive poly(N-isopropylacrylamide-co-benzo-12-crown-4-acrylamide) (PNB12 C4 ) linear copolymers with benzo-12-crown-4 (B12C4) as both guest and host units are prepared. The copolymers exhibit highly selective sensitivities toward γ-cyclodextrin (γ-CD) and Na(+) . The presence of γ-CD induces the lower critical solution temperature (LCST) of PNB12 C4 copolymer to shift to a higher value due to the formation of 1:1 γ-CD/B12C4 host-guest inclusion complexes, while Na(+) causes a negative shift in LCST due to the formation of 2:1 "sandwich" B12C4/Na(+) host-guest complexes. Regardless of the complexation order, when γ-CD and Na(+) coexist with PNB12 C4 , competitive complexation actions of B12C4 as both guest and host units toward γ-CD and Na(+) finally form equilibrium 2:2:1 γ-CD/B12C4/Na(+) composite complexes, and the final LCST values of PNB12 C4 copolymer reach almost the same level. The results provide valuable guidance for designing and applying PNB12 C4 -based smart materials in various applications.

A thermo-responsive hydrogel for body temperature-induced spontaneous information decryption and self-encryption.

A thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel, exhibiting an interesting phenomenon of an opaque-transparent-opaque transition in the successive processes of heating and cooling, is reported. It is fabricated by means of both the porogenic effect of hydroxypropyl cellulose and the cononsolvency effect of PNIPAM in a mixed solvent of dimethyl sulfoxide and water. After being mildly triggered by body temperature, the hydrogel is used to spontaneously decrypt the quick response code within 4 min and then autonomously encrypts the code again within 10 min at room temperature. The mechanism for the transient transparency of hydrogels during the quenching process has been elucidated.

Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

Dissolving microneedle system containing Ag nanoparticle-decorated silk fibroin microspheres and antibiotics for synergistic therapy of bacterial biofilm infection.

Most cases of delayed wound healing are associated with bacterial biofilm infections due to high antibiotic resistance. To improve patient compliance and recovery rates, it is critical to develop minimally invasive and efficient methods to eliminate bacterial biofilms as an alternative to clinical debridement techniques. Herein, we develop a dissolving microneedle system containing Ag nanoparticles (AgNPs)-decorated silk fibroin microspheres (SFM-AgNPs) and antibiotics for synergistic treatment of bacterial biofilm infection. Silk fibroin microspheres (SFM) are controllably prepared in an incompatible system formed by a mixture of protein and carbohydrate solutions by using a mild all-aqueous phase method and serve as biological templates for the synthesis of AgNPs. The SFM-AgNPs exert dose- and time-dependent broad-spectrum antibacterial effects by inducing bacterial adhesion. The combination of SFM-AgNPs with antibiotics breaks the limitation of the antibacterial spectrum and achieves better efficacy with reduced antibiotic dosage. Using hyaluronic acid (HA) as the soluble matrix, the microneedle system containing SFM-AgNPs and anti-Gram-positive coccus drug (Mupirocin) inserts into the bacterial biofilms with sufficient strength, thereby effectively delivering the antibacterial agents and realizing good antibiofilm effect on Staphylococcus aureus-infected wounds. This work demonstrates the great potential for the development of novel therapeutic systems for eradicating bacterial biofilm infections.

Portable diagnosis method of hyperkalemia using potassium-recognizable poly(N-isopropylacrylamide-co-benzo-15-crown-5-acrylamide) copolymers.

A novel, simple, portable, and low-cost method for diagnosis of hyperkalemia by using K(+)-recognizable poly(N-isopropylacrylamide-co-benzo-15-crown-5-acrylamide) [poly(NIPAM-co-B15C5Am)] linear copolymer as indicator is presented in this work. The pendent 15-crown-5 units in the linear copolymers can selectively and specifically recognize K(+) to form stable 2:1 "sandwich" host-guest complexes, which cause the copolymer chains to change from the hydrophilic state to the hydrophobic state isothermally, whereas other tested metal ions (e.g., Li(+), Na(+), Cs(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Cu(2+), Fe(3+), Pb(2+), Cd(2+), Cr(3+)) cannot be recognized. With increasing the 15-crown-5 content or the K(+) concentration, the poly(NIPAM-co-B15C5Am) linear copolymers exhibit higher sensitivity to K(+). The hyperkalemia can be simply diagnosed by observing the K(+)-induced optical transmittance change of human blood samples with poly(NIPAM-co-B15C5Am) linear copolymer as an indicator. Normal blood samples with low potassium level containing the poly(NIPAM-co-B15C5Am) linear copolymer are almost transparent since the copolymer is hydrophilic and soluble at the operating temperature. However, severe hyperkalemia samples with high potassium level become completely cloudy since the copolymer is hydrophobic and insoluble at this temperature. The presented diagnosis method with poly(NIPAM-co-B15C5Am) linear copolymer as indicator is quite simple and low-cost, and it would bring a new candidate material to design simple and portable tools for diagnosis of hyperkalemia in the general population. Moreover, the results in this work provide valuable guidance for building novel poly(NIPAM-co-B15C5Am)-based artificial K(+)-recognizable "smart" or "intelligent" systems in various application fields.

Histological, Physiological and Biomechanical Effects of Low-Level Laser Therapy on Tendon Healing in Animals and Humans: A Systematic Review.

Low-level Laser Therapy (LLLT) was widely used in clinical practice for tendon disorders. However, the underlying mechanisms and effectiveness of LLLT in treating tendon injury remain unclear. Therefore, the present study was conducted aiming to summarize the evidence regarding the histological, physiological, and biomechanical effects of LLLT on tendon healing in animal and human models. Four databases were searched for relevant literature. Four independent reviewers screened abstracts and full-text articles, extracted relevant data, evaluated the risk of bias, and quantified the quality of evidence. Database searches yielded 1400 non-duplicated citations. Fifty-five studies were included (50 animal and five human studies). Animal studies revealed that LT had stimulating effects on collagen organization, collagen I and collagen II formation, matrix metalloproteinase (MMP)-8, transforming growth factor ß1, vascular endothelial growth factor, hydroxyproline, maximum load, maximum elongation before breaking, and tendon stiffness. However, LLLT had inhibitory effects on the number of inflammatory cells, histological scores, relative amount of collagen III, cyclooxygenase-2, prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α, MMP-1, and MMP-3. Although one human study found that LLLT reduced the concentration of PGE2 in peritendinous tissue of the Achilles tendon, other human studies revealed that the effects of LLLT on the physiology and biomechanics of human tendons remained uncertain. LLLT facilitates tendon healing through various histological, physiological, and biomechanical effects in animal models. Only post-LLLT anti-inflammatory effects were found in human studies.

Composite Separable Microneedles for Transdermal Delivery and Controlled Release of Salmon Calcitonin for Osteoporosis Therapy.

A composite separable microneedles (MNs) system consisting of silk fibroin (SF) needle tips and hyaluronic acid (HA) base is developed for transdermal delivery of salmon calcitonin (sCT) for therapy of osteoporosis. Poly(ethylene glycol) (PEG) is used to modulate the conformation structure of SF to achieve controllable sustained release of sCT. The prepared MNs can effectively penetrate the skin stratum corneum. After application to the skin, the HA base is dissolved within 2 min, allowing these SF drug depots to be implanted into the skin for controllable sustained release of sCT. The release kinetics of sCT can be controlled by regulating the conformation of SF with PEG and the interaction between sCT peptide and SF proteins. Compared with traditional needle injection, delivery of sCT using optimized HA-PEG/SF MNs shows better trabecular bone repair for ovariectomized-induced osteoporosis in mice. The proposed MNs system provides a new noninjection strategy for therapy of osteoporosis.

Novel thermo and ion-responsive copolymers based on metallo-base pair directed host-guest complexation for highly selective recognition of Hg2+ in aqueous solution.

The development of materials with highly selective recognition towards Hg2+ is of great significance in environmental monitoring. Herein, a novel thermo-responsive copolymer with Hg2+ recognition property is prepared via thermally-initiated copolymerization of 5'-O-Acryloyl 5-methyl-uridine (APU) and N-isopropylacrylamide (NIPAM). The chemical structure and stimuli-sensitive properties of poly(N-isopropylacrylamide-co-5-methyl-uridine) (P(NIPAM-co-APU)) linear polymers and hydrogel are thoroughly investigated. At the supramolecular level, P(NIPAM-co-APU) linear polymers could respond to both temperature and Hg2+ stimuli with highly selective recognition towards Hg2+ over other 18 metal ion species (at least 5 fold difference) and common anions. Upon capturing Hg2+ by APU units as host metal receptors, the lower critical solution temperature (LCST) of P(NIPAM-co-APU, PNU-7 and PNU-11) linear polymers are significantly shifted more than 10 °C due to the formation of stable APU-Hg2+-APU directed host-guest complexes. Accordingly, at the macroscopic level, P(NIPAM-co-APU) hydrogel display selective and robust recognition of Hg2+ under optimum conditions, and its maximum Hg2+ uptake capacity was 33.1 mg g-1. This work provides a new option for Hg2+ recognition with high selectivity, which could be facilely integrated with other smart systems to achieve satisfactory detection of environmental Hg2+.