Naturally sourced hydrogels: emerging fundamental materials for next-generation healthcare sensing.

The flourishing development of flexible healthcare sensing systems is inseparable from the fundamental materials with application-oriented mechanical and electrical properties. Thanks to continuous inspiration from our Mother Nature, flexible hydrogels originating from natural biomass are attracting growing attention for their structural and functional designs owing to their unique chemical, physical and biological properties. These highly efficient architectural and functional designs enable them to be the most promising candidates for flexible electronic sensing devices. This comprehensive review focuses on the recent advances in naturally sourced hydrogels for constructing multi-functional flexible sensors and healthcare applications thereof. We first briefly introduce representative natural polymers, including polysaccharides, proteins, and polypeptides, and summarize their unique physicochemical properties. The design principles and fabrication strategies for hydrogel sensors based on these representative natural polymers are outlined after the fundamental material properties required in healthcare sensing applications are presented. We then highlight the various fabrication techniques of natural hydrogels for sensing devices, and illustrate the representative examples of wearable or implantable bioelectronics for pressure, strain, temperature, or biomarker sensing in the field of healthcare systems. Finally, concluding remarks on challenges and prospects in the development of natural hydrogel-based flexible sensors are provided. We hope that this review will provide valuable information for the development of next-generation bioelectronics and build a bridge between the natural hydrogels as fundamental matter and multi-functional healthcare sensing as an applied target to accelerate new material design in the near future.

Antimicrobial Lignin-Based Polyurethane/Ag Composite Foams for Improving Wound Healing.

Antimicrobial materials are an urgent need for modern wound care in the clinic. Although traditional polyurethane foams have proven to be clinically valuable for wound treatment, their petroleum-originated preparation and bioinert nature have restricted their efficacy in biomedical applications. Here, we propose a simple one-step foaming method to prepare lignin-based polyurethane foams (LPUFs) in which fully biobased polyether polyols partially replace traditional petroleum-based raw materials. The trace amount of phenolic hydroxyl groups (about 4 mmol) in liquefied lignin acts as a direct reducing agent and capping agent to silver ions (less than 0.3 mmol), in situ forming silver nanoparticles (Ag NPs) within the LPUF skeleton. This newly proposed lignin polyurethane/Ag composite foam (named as Ag NP-LPUF) shows improved mechanical, thermal, and antibacterial properties. It is worth mentioning that the Ag NP-LPUF exhibits more than 99% antibacterial rate against Escherichia coli within 1 h and Staphylococcus aureus within 4 h. Evaluations in mice indicate that the antimicrobial composite foams can effectively promote wound healing of full-thickness skin defects. As a proof of concept, this antibacterial and biodegradable foam exhibits significant potential for clinical translation in wound care dressings.

De Novo Design of Entropy-Driven Polymers Resistant to Bacterial Attachment via Multicomponent Reactions.

Nonbactericidal polymers that prevent bacterial attachment are important for public health, environmental protection, and avoiding the generation of superbugs. Here, inspired by the physical bactericidal process of carbon nanotubes and graphene derivatives, we develop nonbactericidal polymers resistant to bacterial attachment by using multicomponent reactions (MCRs) to introduce molecular "needles" (rigid aliphatic chains) and molecular "razors" (multicomponent structures) into polymer side chains. Computer simulation reveals the occurrence of spontaneous entropy-driven interactions between the bacterial bilayers and the "needles" and "razors" in polymer structures and provides guidance for the optimization of this type of polymers for enhanced resistibility to bacterial attachment. The blending of the optimized polymer with commercially available polyurethane produces a film with remarkably superior stability of the resistance to bacterial adhesion after wear compared with that of commercial mobile phone shells made by the Sharklet technology. This proof-of-concept study explores entropy-driven polymers resistant to bacterial attachment via a combination of MCRs, computer simulation, and polymer chemistry, paving the way for the de novo design of nonbactericidal polymers to prevent bacterial contamination.

The Hantzsch Reaction in Polymer Chemistry: From Synthetic Methods to Applications.

The Hantzcsh reaction is a robust four-component reaction for the efficient generation of 1,4-dihydropyridine (1,4-DHP) derivatives. Recently, this reaction has been introduced into polymer chemistry in order to develop polymers having 1,4-DHP structures in the main and/or side chains. The 1,4-DHP groups confer new properties/functions to the polymers. This mini-review summarizes the recent studies on the development of new functional polymers by using the Hantzsch reaction. Several synthetic approaches, including polycondensation, post-polymerization modification (PPM), monomer to polymer strategy, and one-pot strategy are introduced; different applications (protein conjugation, formaldehyde detection, drug carrier, and anti-bacterial adhesion) of the resulting polymers are emphasized. Meanwhile, the future development of the Hantzsch reaction in exploring new functional polymers is also discussed.

Recent Advances on Fabrication of Polymeric Composites Based on Multicomponent Reactions for Bioimaging and Environmental Pollutant Removal.

As the core of polymer chemistry, manufacture of functional polymers is one of research hotspots over the past several decades. Various polymers are developed for diverse applications due to their tunable structures and unique properties. However, traditional step-by-step preparation strategies inevitably involve some problems, such as separation, purification, and time-consuming. The multicomponent reactions (MCRs) are emerging as environmentally benign synthetic strategies to construct multifunctional polymers or composites with pendant groups and designed structures because of their features, such as efficient, fast, green, and atom economy. This mini review summarizes the latest advances about fabrication of multifunctional fluorescent polymers or adsorptive polymeric composites through different MCRs, including Kabachnik-Fields reaction, Biginelli reaction, mercaptoacetic acid locking imine reaction, Debus-Radziszewski reaction, and Mannich reaction. The potential applications of these polymeric composites in biomedical and environmental remediation are also highlighted. It is expected that this mini-review will promote the development preparation and applications of functional polymers through MCRs.

Low-Tortuosity Water Microchannels Boosting Energy Utilization for High Water Flux Solar Distillation.

Solar distillation through photothermal evaporators has approached solar light energy (E1) limit under no solar concentration but still suffers from modest vapor and clean water production. Herein, a nature-inspired low-tortuosity three-dimensional (3D) evaporator is demonstrated to significantly improve water production. The solar evaporator, prepared from polypyrrole-modified maize straw (PMS), had upright vascular structures enabling high water lifting and horizontal microgaps facilitating broad water distribution to the out-surface. Consequently, this novel PMS evaporator dramatically enhanced the utilization of the solar heat energy stored in the environment (E2) for promoting evaporation. The maximum vapor generation rate of a single PMS respectively increases 2.5 and 6 times compared with the conventional 3D evaporators and the planar evaporators of an identical occupied area. Consequently, a scaled-up PMS array achieved a state-of-the-art vapor generation rate of 3.0 L m-2 h-1 (LMH) under a simulated condition and a record-high clean water production of 2.2 LMH for actual seawater desalination under natural conditions (1 sun intensity). This breakthrough reveals great potentials for cost-effective freshwater production as well as the rational design of high-performance photothermal evaporators for solar distillation.

A Facile Preparation of Mussel-Inspired Poly(dopamine phosphonate-co-PEGMA)s via a One-Pot Multicomponent Polymerization System.

Mussel-inspired polymers attract much research interest due to their potential as effective adhesives. In this work, a new kind of mussel-inspired polymer, poly(dopamine phosphonate-co-PEGMA), is prepared via a one-pot multicomponent polymerization system. The multicomponent polymerization system refers to a combination of multicomponent Kabachnik-Fields (KF) reaction and reversible addition-fragmentation chain transfer (RAFT) polymerization system. Reactants are converted to dopamine phosphonate monomers in situ through the KF reaction and polymerized simultaneously along with poly(ethylene glycol methyl ether) methacrylate (PEGMA) co-monomers by the RAFT process in a one-pot operation. Target polymers with dopamine phosphonate as side groups and well-defined polymer structures are thus facilely and successfully prepared. Afterwards, a series of polymers with various ratios of dopamine phosphonates as well as the crosslinked polymer analogues are prepared. Benefiting from the dopamine phosphonate side groups, aqueous solutions of those polymers show potential as effective adhesives in both dry and wet conditions, and their adhesive strengths are highly related to ratios of dopamine phosphonates in the polymers. Those polymers are non-cytotoxic and show strong bonding affinities on various substrates including metals, polymers, and bovine bones, suggesting their potential as environmentally friendly general adhesives in broad areas.

Recent Advances and Progress on Melanin-like Materials and Their Biomedical Applications.

Melanins are well-known biopolymers that are ubiquitous in nature, distributed widely in microorganisms, plants, and animals, and play significant physiological roles. They are mostly biopolymers formed from phenolic compounds by polymerization via quinones. Poly(dopamine) (PDA), a melanin-like material, is similar in structure and properties to eumelanin and has attracted considerable interest for various types of biological applications. This review outlines the recent advances in the structure and synthesis of PDA and discusses applications of PDA in many biological fields, such as biological imaging, photothermal therapy, and drug delivery systems. The purpose of this review is to give a brief overview of the synthesized procedures, structure, biomedical applications, and prospects of melanin-like materials.

Synthesis of Starch-Based Amphiphilic Fluorescent Nanoparticles and Their Application in Biological Imaging.

Due to the extensive source, good biocompatibility and biodegradability, the starch of carbohydrates has been extensively investigated for application in biological field. Recently, the development of fluorescent organic nanoparticles (FONs) on the basis of aggregation induced emission (AIE) dyes has attracted great research interest. In this article, novel starch-based S-TPEV polymers with AIE property were successfully fabricated by atom transfer radical polymerization (ATRP) of TPEV dye into water-soluble starch for the first time, subsequently, their structure and properties were detailedly investigated by 1H NMR, TEM, UV-vis, FL and FTIR. The characterization results confirmed the successful synthesis of S-TPEV polymers, and the molar fraction of TPEV and C6H10O5 ring in the starch polymers could be respectively calculated as approximate 5.8% and 94.2%. In aqueous solution, the as-prepared S-TPEV polymers will tend to self-assemble into FONs with 100-200 nm diameters, and their fluorescence intensity increased with the increase of the concentration of water in the mixed solution of water and DMSO, indicative of the obvious AIE property. More importantly, owing to their high water dispersity, good fluorescence and excellent biocompatibility, the S-TPEV FONs can be uptaken by HepG2 cells and show promising application in biological imaging field.

Injectable and Self-Healing Chitosan Hydrogel Based on Imine Bonds: Design and Therapeutic Applications.

Biological tissues can automatically repair themselves after damage. Examples include skin, muscle, soft tissue, etc. Inspired by these living tissues, numerous self-healing hydrogels have been developed recently. Chitosan-based self-healing hydrogels constructed via dynamic imine bonds have been widely studied due to their simple preparation, good biocompatibility, and automatic reparability under physiological conditions. In this mini-review, we highlighted chitosan-based self-healing hydrogels based on dynamic imine chemistry, and provided an overview of the preparation of these hydrogels and their bioapplications in cell therapy, tumor therapy, and wound healing.

Recent Advances and Future Prospects of Aggregation-induced Emission Carbohydrate Polymers.

Aggregation-induced emission (AIE) is an abnormal phenomenon that has sparked great attention for diverse applications in different fields. In particular, the fabrication and biological imaging applications of AIE-active fluorescent organic nanoparticles (FONs) have become a focus in the emerging and promising fields. A large number of AIE-active polymeric nanoprobes have recently been fabricated through different strategies. The advances and progress in this direction have also recently been summarized by some groups. However, the fabrication and biomedical applications of AIE-active FONs based on carbohydrate polymers and AIE-active dyes are quite rare and limited. In this feature article, the recently reported AIE-active FONs with different structures and applications based on AIE-active dyes and carbohydrate polymers are highlighted, and the major current limitations and development tendencies are also discussed.

3D Printing of Aniline Tetramer-Grafted-Polyethylenimine and Pluronic F127 Composites for Electroactive Scaffolds.

Electroactive hydrogel scaffolds are fabricated by the 3D-printing technique using composites of 30% Pluronic F127 and aniline tetramer-grafted-polyethylenimine (AT-PEI) copolymers with various contents from 2.5% to 10%. The synthesized AT-PEI copolymers can self-assemble into nanoparticles with the diameter of ≈50 nm and display excellent electroactivity due to AT conjugation. The copolymers are then homogeneously distributed into 30% Pluronic F127 solution by virtue of the thermosensitivity of F127, denoted as F/AT-PEI composites. Macroscopic photographs of latticed scaffolds elucidate their excellent printability of F/AT-PEI hydrogels for the 3D-printing technique. The conductivities of the printed F/AT-PEI scaffolds are all higher than 2.0 × 10-3 S cm-1 , which are significantly improved compared with that of F127 scaffold with only 0.94 × 10-3 S cm-1 . Thus, the F/AT-PEI scaffolds can be considered as candidates for application in electrical stimulation of tissue regeneration such as repair of muscle and cardiac nerve tissue.

Facile Fabrication of AIE-Active Fluorescent Polymeric Nanoparticles with Ultra-Low Critical Micelle Concentration Based on Ce(IV) Redox Polymerization for Biological Imaging Applications.

Fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) property have received increasing attention and possess promising biomedical application potential in the recent years. Many efforts have been devoted to the fabrication methodologies of FPNs and significant advance has been achieved. In this contribution, a novel strategy for the fabrication of AIE-active amphiphilic copolymers is reported for the first time based on the Ce(IV) redox polymerization. As an example, ene group containing AIE-active dye (named as Phe-alc) is directly grafted onto a water soluble polymer polyethylene glycol (PEG) in H2 O/THF system under low temperature. Thus-obtained amphiphilic fluorescent polymers will self-assemble into FPNs with ultra-low critical micelle concentration, ultra-brightness, and great water dispersibility. Biological evaluation results suggest that the PEG-poly(Phe-alc) possess excellent biocompatibility and can be used for tracing their behavior in cells using confocal laser scanning microscope. These features make PEG-poly(Phe-alc) FPNs promising candidates for many biomedical applications, such as cell imaging, drug delivery vehicles, and targeted tracing. More importantly, many other functional groups can also be incorporated into these AIE-active FPNs through the redox polymerization. Therefore, the redox polymerization should be a facile and effective strategy for fabrication of AIE-active FPNs.

Shape Changes and Interaction Mechanism of Escherichia coli Cells Treated with Sericin and Use of a Sericin-Based Hydrogel for Wound Healing.

UNLABELLED: To verify the interaction mechanism between sericin and Escherichia coli, especially the morphological and structural changes in the bacterial cells, the antimicrobial activity of sericin against E. coli as a model for Gram-negative bacteria was investigated. The antibacterial activity of sericin on E. coli and the interaction mechanism were investigated in this study by analyzing the growth, integrity, and morphology of the bacterial cells following treatment with sericin. The changes in morphology and cellular compositions of bacterial cells treated with sericin were observed by an inverted fluorescence microscope, scanning electron microscopy, and transmission electron microscopy. Changes in electrical conductivity, total sugar concentration of the broth for the bacteria, and protein expression of the bacteria were determined to investigate the permeability of the cell membrane. A sericin-based hydrogel was prepared for an in vivo study of wound dressing. The results showed that the antibacterial activity of the hydrogel increased with the increase in the concentration of sericin from 10 g/liter to 40 g/liter. The introduction of sericin induces membrane blebbing of E. coli cells caused by antibiotic action on the cell membrane. The cytoplasm shrinkage phenomenon was accompanied by blurring of the membrane wall boundaries. When E. coli cells were treated with sericin, release of intracellular components quickly increased. The electrical conductivity assay indicated that the charged ions are reduced after exposure to sericin so that the integrity of the cell membrane is weakened and metabolism is blocked. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that sericin hinders the expression of bacterial protein. Sericin may damage the integrity of the bacterial cell membrane, thereby eventually inhibiting the growth and reproduction of E. coli Compared to sterile gauze, the sericin-based hydrogel promoted fibroblast cell proliferation and accelerated the formation of granulation tissues and neovessels. IMPORTANCE: The specific relationship and interaction mechanism between sericin and E. coli cells were investigated and elucidated. The results show that after 12 h of treatment, sericin molecules induce membrane blebbing of E. coli cells, and the bacteria show decreases in liquidity and permeability of biological membrane, resulting in alterations in the conductivity of the culture medium and the integrity of the outer membrane. The subsequent in vivo results demonstrate that the sericin-poly(N-isopropylacrylamide-N,N'-methylene-bis-acrylamide [NIPAm-MBA]) hydrogel accelerated wound healing compared to that with sterile gauze, which is a beneficial result for future applications in clinical medicine and the textile, food, and coating industries.

Facile Fabrication of PEGylated Fluorescent Organic Nanoparticles with Aggregation-Induced Emission Feature via Formation of Dynamic Bonds and Their Biological Imaging Applications.

Driven by the high demand for sensitive and specific tools for optical imaging, fluorescent nanoprobes with various working mechanisms and advanced functionalities are flourishing at an incredible speed. This work reports the design and fabrication of aggregation-induced emission (AIE)-active fluorescent organic nanoparticles (FNPs) via forming dynamic phenyl borate between diol containing hydrophobic AIE dye (APD-PhCHO) and phenylboronic acid pendant hydrophilic polymers (PEGMA-VPBA) within 30 min. The final AIE-active APD-PhCHO-PEGMA-VPBA FNPs display high water dispersibility and strong fluorescence emission because of their amphiphilic properties and AIE feature. Biological evaluation suggests that APD-PhCHO-PEGMA-VPBA FNPs possess negative effect on HeLa cells and desirable optical properties for biological imaging. More importantly, phenyl borate is a dynamic bond with pH and glucose responsiveness. Furthermore, different functions can be designed and introduced into these AIE-active systems through adoption of different monomers for good applicability of free radical polymerization. Therefore, this work provides a novel platform for preparation of multifunctional AIE-active nanosystems with responsiveness for various biomedical applications.

In vitro study of electroactive tetraaniline-containing thermosensitive hydrogels for cardiac tissue engineering.

Injectable hydrogels made of degradable biomaterials can function as both physical support and cell scaffold in preventing infarct expansion and promoting cardiac repair in myocardial infarction therapy. Here, we report in situ hydrogels consisting of thermosensitive PolyNIPAM-based copolymers and electroactive tetraaniline (TA). Studies showed that the addition of 2-methylene-1,3-dioxepane (MDO) provided the PolyNIPAM-based gel with biodegradability, and the introduction of tetraaniline endowed these copolymers with desirable electrical properties and antioxidant activities. The encapsulated H9c2 cells (rat cardiac myoblast) remained highly viable in the gel matrices. In vivo gel formation and histological analyses were performed in rats by subcutaneous injection and excellent biocompatibility was observed. Furthermore, the proliferation and intracellular calcium transients of H9c2 cells were also studied with (and without) electrical stimuli. Both in vitro and in vivo results demonstrated that electroactive hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering.

In vitro studies on regulation of osteogenic activities by electrical stimulus on biodegradable electroactive polyelectrolyte multilayers.

In this study, a novel electroactive tetreaniline-containing degradable polyelectrolyte multilayer film (PEM) coating [(poly(l-glutamic acid)-graft-tetreaniline/poly(l-lysine)-graft-tetreaniline)n, (PGA-g-TA/PLL-g-TA)n] was designed and fabricated by layer-by-layer (LbL) assembly method. Compared with the nongrafted PEMs, the tetreaniline-grafted PEMs showed higher roughness and stiffness in micro/nanoscale structures. The special surface characteristics and the typical electroconductive properties were more beneficial for adhesion, proliferation, and differentiation of preosteoblast MC3T3-E1 cells. Moreover, the enhanced effects were observed on the modulation of MC3T3-E1 cells that differentiated into maturing osteoblasts, when the electroactive PEMs were coupled with electrical stimulus (ES), especially in the early phase of the osteoblast differentiation. The alkaline phosphatase (ALP) activity, calcium deposition, immunofluorescence staining, and RT-qPCR were evaluated on the differentiation of preosteoblast. These data indicate that the comprehensive effects through coupling electroactive scaffolds with electrical stimulus are better to develop bioelectric strategies to control cell functions for bone regeneration.

Stable cross-linked fluorescent polymeric nanoparticles for cell imaging.

Aggregation-induced emission (AIE) dye-based cross-linked fluorescent polymeric nanoparticles (FPNs) are facilely prepared via a two-step polymerization process including emulsion polymerization and subsequent anhydride cross-linking. Then, a variety of characterization methods are carried out to determine the performance of the FPNs, which show high dispersibility and strong fluorescence in an aqueous solution due to the hydrophilic carboxyl groups on the surfaces and the AIE components as the cores. Biocompatibility evaluation and cell imaging results suggest that these FPNs are biocompatible for cell imaging. More importantly, this cross-linking strategy is proven to overcome the issue of critical micelle concentration and opens the opportunity to develop more robust fluorescent bioprobes.

Wormwood-infused porous-CaCO3 for synthesizing antibacterial natural rubber latex.

Wormwood leaf is a traditional Chinese herbal medicine with a high medicinal value and long application history and its essential oil is a high-purity plant oil extracted from Wormwood leaf. Pharmacological research reveals that Wormwood leaf and Wormwood essential oil are a broad-spectrum antibacterial and antiviral drug, which can inhibit and kill many bacteria and viruses. We loaded wormwood extract on porous calcium carbonate (Porous-CaCO3) and introduced it and Wormwood essential oil into Natural rubber latex (NRL), thus synthesizing NRL composites with excellent vitro and in vivo antibacterial effect, cell compatibility and mechanical properties. This NRL material can delay the light aging and thermal oxidation of some mechanical properties, which provides a broader avenue for its commercialization.

Synthesis of an aggregation-induced emission (AIE) dye with pH-sensitivity based on tetraphenylethylene-pyridine for fluorescent nanoparticles and its applications in bioimaging and in vitro anti-tumor effect.

In this contribution, a novel AIE monomers 2-(4-styrylphenyl)- 1,2-diphenylvinyl)styryl)pyridine (SDVPY) with smart fluorescent pH-sensitivity basing on tetraphenylethylene-pyridine were successfully synthesized for the first time, subsequently, a series of amphiphilic copolymers PEG-PY were achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of SDVPY and poly(ethylene glycol) methacrylate (PEGMA), which would self-assemble in water solution to form core-shell nanoparticles (PEG-PY FONs) with about 150 nm diameter. The PEG-PY FONs showed obvious fluorescence response to Fe3+, HCO3- and CO32- ions in aqueous solution owing to their smart pH-sensitivity and AIE characteristics, and their maximum emission wavelength could reversibly change from 525 nm to 624 nm. The as-prepared PEG-PY FONs showed also prospective application in cells imaging with the variable fluorescence for different pH cells micro-environment. When PEG-PY copolymers self-assembled with the anti-tumor drug paclitaxel (PTX), the obtained PY-PTX FONs could effectively deliver and release PTX with pH-sensitivity, and could be easily internalized by A549 cells and located at the cytoplasm with high cytotoxicity, which was further confirmed by the Calcein-AM/PI staining of dead and alive A549 cells. Moreover, the flow cytometry results indicated that the PY-PTX FONs could obviously induce the apoptosis of A549 cells, which further showed the great potential of PY-PTX FONs in the application of tumors therapy.