Semiconvertible Hyaluronic Hydrogel Enabled Red-Light-Responsive Reversible Mechanics, Adhesion, and Self-Healing.

Photoresponsive supramolecular hydrogels based on the host-guest interaction between cyclodextrin (CD) and azobenzene (Azo) are highly favored in "on-demand" biological applications. Nevertheless, most Azo/CD-based hydrogels are UV-responsive, exhibiting poor tissue penetrability and potential cytotoxicity; more importantly, the complete gel-sol transition under irradiation makes intelligent systems unstable. Here, we report a red-light-responsive semiconvertible hydrogel based on tetra-ortho-methoxy-substituted Azo (mAzo)- and CD-functionalized hyaluronic acid (HA). By integrating red-shifted-photoisomerized mAzo with HA, a biocompatible 625 nm-light-responsive polymeric guest with strengthened hydrogen bonding and weakened photoisomerization was synthesized. Upon alternating irradiation, mAzo-HA/CD-HA hydrogels obtained here exhibited reversible mechanical and structural dynamics, while avoiding complete gel-sol transition. This improved semiconvertibility remedies the lack of macroscopic resilience for dynamic system so as to endow supramolecular hydrogels with spatial-temporal mechanics, self-healing, and adhesion. Together with excellent cytocompatibility and manufacturability, these hydrogels show potential advantages in tissue engineering, especially for the regeneration of functional multi-tissue complex.

Synthesis and Characterization of a Novel Borazine-Type UV Photo-Induced Polymerization of Ceramic Precursors.

A preceramic polymer of B,B',B''-(dimethyl)ethyl-acrylate-silyloxyethyl-borazine was synthesized by three steps from a molecular single-source precursor and characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectrometry. Six-member borazine rings and acrylate groups were effectively introduced into the preceramic polymer to activate UV photo-induced polymerization. Photo-Differential Scanning Calorimetry (Photo-DSC) and real-time FTIR techniques were adapted to investigate the photo-polymerization process. The results revealed that the borazine derivative exhibited dramatic activity by UV polymerization, the double-bond conversion of which reached a maximum in 40 s. Furthermore, the properties of the pyrogenetic products were studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD), which proved the ceramic annealed at 1100 °C retained the amorphous phase.

Flexible silk-fibroin-based microelectrode arrays for high-resolution neural recording.

High-precision neural recording plays a pivotal role in unraveling the intricate mechanisms that underlie information transmission of the nervous system, raising increasing interest in the development of implantable microelectrode arrays (MEAs). The challenge lies in providing a truly soft, highly conductive and low-impedance neural interface for precise recording of the electrophysiological signals of individual neurons or neural networks. Herein, by implementing a novel topological regulation strategy of silk fibroin (SF) crosslinking, we prepared a flexible, hydrophilic, and biocompatible MEA substrate, facilitating a biocompatible neural interface that minimizes mechanical mismatch with biological tissues. Additionally, we established a strategy involving screen-printing combined with post-coating to prepare MEAs with high conductivity, low impedance and high capacitance, by coating PEDOT:PSS on titanium carbide (Ti3C2) microarrays. The Ti3C2 nanosheets, as the conductive track of the MEAs, avoided the charge drifting associated with metals and facilitated the processing of the MEAs. Further coating PEDOT:PSS on the electrode points reduced the impedance 100-fold, from 105 to 103 Ω. Experimental validation confirmed the superior electrophysiological signal recording capabilities of the SF-based MEA (SMEA) in peripheral and cerebral nerves with a much higher signal-to-noise ratio (SNR) of 20. In particular, we achieved high-precision recording of the action potential (AP) induced by flash visual stimulation, demonstrating high performance in weak signal recording. In summary, the development of SMEA provides a robust foundation for future investigations into the mechanisms and principles of neural circuit information transmission in complex nervous systems.

Flexible and temperature-responsive hydrogel dressing for real-time and remote wound healing monitoring.

Wound management is highly clinically desirable due to the complexity and diversity of the wound repair process. However, it is still a major clinical challenge to develop a wound dressing with the capabilities of real-time and remote monitoring during wound healing. Herein, we have designed a polymer-based wound dressing in the form of a conductive, soft, temperature-responsive, antibacterial and biocompatible hydrogel, which is composed of polyacrylic acid (PAA)-grafted poly(N-isopropylacrylamide) (PNIPAM), vinyl-based polyacrylamide (PAM) and silver nanowires (AgNWs). In this hydrogel dressing, PAA-grafted PNIPAM acts as conformal interface and intrinsic temperature-responsive matrix, PAM helps to construct semi-penetrating polymer networks (SIPNs) to improve the mechanical properties, while the AgNWs introduce a three-dimensional conductive hydrogel network with antibacterial properties and sensing properties. The constructed hydrogel matrix was connected to a Bluetooth module to transmit the temperature changes wirelessly to a smart device. The design integrating a conductive hydrogel dressing with a wireless transmission module realized the real-time and wireless monitoring of the wound temperature, which is helpful to provide an early diagnosis of infection. This proof-of-concept study is highly promising in the development of new strategies to significantly improve wound management and other pathological diagnostics or treatments.

Hydrogen-bonding topological remodeling modulated ultra-fine bacterial cellulose nanofibril-reinforced hydrogels for sustainable bioelectronics.

Bacterial cellulose (BC) with its inherent nanofibrils framework is an attractive building block for the fabrication of sustainable bioelectronics, but there still lacks an effective and green strategy to regulate the hydrogen-bonding topological structure of BC to improve its optical transparency and mechanical stretchability. Herein, we report an ultra-fine nanofibril-reinforced composite hydrogel by utilizing gelatin and glycerol as hydrogen-bonding donor/acceptor to mediate the rearrangement of the hydrogen-bonding topological structure of BC. Attributing to the hydrogen-bonding structural transition, the ultra-fine nanofibrils were extracted from the original BC nanofibrils, which reduced the light scattering and endowed the hydrogel with high transparency. Meanwhile, the extracted nanofibrils were connected with gelatin and glycerol to establish an effective energy dissipation network, leading to an increase in stretchability and toughness of hydrogels. The hydrogel also displayed tissue-adhesiveness and long-lasting water-retaining capacity, which acted as bio-electronic skin to stably acquire the electrophysiological signals and external stimuli even after the hydrogel was exposing to air condition for 30 days. Moreover, the transparent hydrogel could also serve as a smart skin dressing for optical identification of bacterial infection and on-demand antibacterial therapy after combined with phenol red and indocyanine green. This work offers a strategy to regulate the hierarchical structure of natural materials for designing skin-like bioelectronics toward green, low cost, and sustainability.

Dopamine induced multiple bonding in hyaluronic acid network to construct particle-free conductive hydrogel for reliable electro-biosensing.

Conductive hydrogel (CH) as flexible electrophysiology interface has become the new trend of bioelectronics, but still challenging in synergizing the biocompatibility, mechanics and comprehensive electrical performance. Hyaluronic acid (HA), featured with abundant active sites for personalized-modification and well-known biocompatibility, is one of the alterative candidates. The obstacle lies in the unstable conductivity from the ionic conduction, and the electronic conduction by embedding conductive nanoparticles (NPs) is likely to result in inhomogeneous CH with poor stretchability and discontinuous conductive network. Herein, inspired by catechol chemistry, dopamine (DA)-modified HA was homogeneously composited with DA-modified poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS, named PP), to produce particle-free conductive hydrogel (HA-DA-PP). The DA-introduced multiple bondings in HA network and PP molecules brought aqueous conductive PP into HA hydrogel to form a homogeneous crosslinking network, imparted the flexible stretchability. By accurately regulation, HA-DA-PP achieved high stretchability with large tensile deformation (over 470 %) in the category of natural polymer-based hydrogels. Moreover, the interaction between DA and PP (conformational transition and charge transfer) could effectively enhance the hydrogel's conductivity. Consequently, HA-DA-PP hydrogel showed high sensibility to human movement, epidermal and in vivo electrophysiological signals monitoring. Overall, DA-mediated multiple bonding is a powerful strategy for constructing CH with high performance for bioelectronics.

Clinical Observation of Flapless Implantation in the Posterior Tooth Area under the Guidance of the Fully Guided Template.

Objective: Compared with the conventional flap implantation, the postoperative effect of flapless implantation of a single posterior tooth under the guidance of the fully guided template was observed. Materials and Methods: 67 cases were divided into the template group (n = 35) and the flap group (n = 32) according to the wishes and actual situation of the patients. In the template group, the fully guided template was made by rapid prototyping technology, and the flapless implantation was performed under the guidance of the template in the posterior tooth area. The flap group underwent routine flap implantation. After the operation, the template group took CBCT (cone beam computed tomography) again and fitted it with that before the operation. Neck deviation, apical deviation, depth deviation, and axial angle deviation in buccolingual and mesiodistal directions were measured to observe the accuracy of the fully guided template. At the same time, the postoperative reactions of the two surgical methods were compared by recording the operation time, pain degree 24 hours after the operation, swelling degree 72 hours after the operation, and postoperative satisfaction of patients. Results: Whether in buccolingual or mesiodistal directions, the maximum values of neck deviation, apical deviation, and depth deviation were less than 2 mm. The axial angle deviation was 0.07°âˆ¼5.93° in the buccolingual direction and 0°âˆ¼4.12° in the mesiodistal direction. The guiding effect of the template was relatively reliable, and the implantation site and depth were well controlled. Although there were small deviations, the accuracy of the template could meet the clinical needs. The operation time and the VAS (visual analogue scale) score 24 hours after the operation in the template group were lower than those in the flap group (P < 0.05), and the swelling degree rating 72 hours after the operation and postoperative satisfaction of the patients were better than those in the flap group (P < 0.05). Conclusion: Compared with the conventional flap implantation, the flapless implantation in the posterior tooth area under the guidance of the fully guided template could improve the accuracy of the operation, shorten the operation time, and reduce the degree of postoperative pain and swelling, which had a certain positive clinical significance.

Highly digestible nitrogen-enriched straw upgraded by ozone-urea pretreatment: Digestibility metrics and energy-economic analysis.

Ozone is a powerful oxidative gas widely used as a green pretreatment to enhance the delignification of cereal straws. Urea pretreatment can enrich straws with nitrogen to make them more accessible to anaerobic microorganisms. This study aimed to evaluate the effect of ozone-urea pretreatment on the digestibility of wheat straw (i.e., physicochemical, nitrogen enrichment, gas production, nutritional value, and surface chemistry). The results of ozone-urea pretreatment were compared with non-pretreated, ozone-pretreated, and urea-pretreated samples. This pretreatment method outperformed the other methods in terms of digestibility metrics. The ozone-urea pretreatment resulted in a 50% reduction in lignin, a 4.2 times increase in crude protein, a 22.5% increase in bonded organic-N, a 2 times increase in 24 h-gas production, and a 43.67% increase in total digestible nutrients compared to the non-pretreated sample. Based on the total digestible nutrients index, one-tonne ozone-urea-pretreated straw would be 70.6 USD cheaper than the non-pretreated one.

Spatiotemporal regulation of dynamic cell microenvironment signals based on an azobenzene photoswitch.

Dynamic biochemical and biophysical signals of cellular matrix define and regulate tissue-specific cell functions and fate. To recapitulate this complex environment in vitro, biomaterials based on structural- or degradation-tunable polymers have emerged as powerful platforms for regulating the "on-demand" cell-material dynamic interplay. As one of the most prevalent photoswitch molecules, the photoisomerization of azobenzene demonstrates a unique advantage in the construction of dynamic substrates. Moreover, the development of azobenzene-containing biomaterials is particularly helpful in elucidating cells that adapt to a dynamic microenvironment or integrate spatiotemporal variations of signals. Herein, this minireview, places emphasis on the research progress of azobenzene photoswitches in the dynamic regulation of matrix signals. Some techniques and material design methods have been discussed to provide some theoretical guidance for the rational and efficient design of azopolymer-based material platforms. In addition, considering that the UV-light response of traditional azobenzene photoswitches is not conducive to biological applications, we have summarized the recent approaches to red-shifting the light wavelength for azobenzene activation.

NIR-responsive multi-healing HMPAM/dextran/AgNWs hydrogel sensor with recoverable mechanics and conductivity for human-machine interaction.

Conductive and self-healing hydrogel sensor is perspective in human-machine interaction applications. However, the design of ideal self-healing hydrogels are always challenging. Herein, by introducing disulfide modified Ag nanowires (AgNWs), we show a novel self-healing hydrogel strain sensor with superior mechanics, conductivity, antibacterial property, and firstly realizing of self-healing with both recovery of mechanics and sensing properties. We demonstrate that the covalent and reversible non-covalent hydrophobic blocks in hydrophobic modified polyacrylamide (HMPAM) achieves the basic self-healing network; dextran with plentiful hydroxyl groups synergistic helps the self-healing by hydrogen bonds; disulfide on the AgNWs surface forms a NIR-responsive and dynamic Ag-S coordination bridge between HMPAM and AgNWs. The resulted hydrogel sensor exhibits comprehensive electromechanical properties, and precisely monitors human motion and subtle electromyography (EMG) signals. Importantly, we firstly achieved the recovery of sensing properties on human motion detection and EMG signal detection after self-healing. This work provides a promising exploration to manufacture bionic strain sensors for potential applications in wearable electronics.

A one-pot synthesis of multifunctional Bi2S3 nanoparticles and the construction of core-shell Bi2S3@Ce6-CeO2 nanocomposites for NIR-triggered phototherapy.

As a direct thin band gap n-type semiconductor, bismuth sulfide (Bi2S3) nanomaterials possess great near-infrared (NIR)-triggered photothermal effects, photoacoustic (PA) and computed tomography (CT) imaging properties. Hence, Bi2S3 nanomaterials have become a research focal point in multiple domains, such as the construction of NIR-triggered nanosystems for cancer therapy. In this study, through a simple one-pot synthesis with the assistance of EDTA-2Na, we first obtained monodispersed spherical Bi2S3 of uniform particle sizes with fascinating photothermal and PA/CT imaging properties. Based on this, we introduced the photosensitizer Ce6 with photodynamic property and CeO2 with the O2-evolving characteristic, and thus designed a core-shell structure of the Bi2S3@Ce6-CeO2 nanocomposites (Bi2S3@Ce6-CeO2 NCs). The as-received Bi2S3@Ce6-CeO2 NCs exhibited a remarkable synergetic photothermal and photodynamic therapeutic effect both in vitro and in vivo, demonstrating its promising potential for cancer treatments. In the long term, the multifunctional PA/CT properties of both Bi2S3 NPs and Bi2S3@Ce6-CeO2 NCs in this study also supply a novel Bi2S3-based platform for constructing integrated diagnosis and treatment platforms.

Biofabrication of nerve fibers with mimetic myelin sheath-like structure and aligned fibrous niche.

Nerve tissues contain hierarchically ordered nerve fibers, while each of the nerve fibers has nano-oriented fibrous extracellular matrix and a core-shell structure of tubular myelin sheath with elongated axons encapsulated. Here, we report, for the first time, a ready approach to fabricate biomimetic nerve fibers which are oriented and have a core-shell structure to spatially encapsulate two types of cells, neurons and Schwann cells. A microfluidic system was designed and assembled, which contained a coaxial triple-channel chip and a stretching loading device. Alginate was used first to assist the fabrication, which was washed away afterwards. The orientation of the biomimetic nerve fibers was optimized by the control of the compositions of methacrylate hyaluronan and fibrin, together with the parameters of microfluidic shearing and external stretching. Also, neurons and Schwann cells, which were respectively located in the core and shell of the fibers, displayed advanced biologic functions, including neurogenesis and myelinating maturation. We demonstrate that the neural performance is relatively good, compared to that resulted from individually encapsulated in single-layer microfibers. The present study brings insights to fabricate biomimetic nerve fibers for their potential in neuroscience research and nerve regeneration. Moreover, the present methodology on the fabrication of oriented fibers with different types of cells separately encapsulated should be applicable to biomimetic constructions of various tissues.

Designing a castor oil-based polyurethane as bioadhesive.

Based on the stealth behavior of castor oil and poly(ethylene glycol), we selected a polyurethane system to obtain an ideal surgical adhesive. The polyurethane adhesives with varying concentrations of castor oil were investigated by Fourier transform infrared spectrometer, differential scanning calorimetry, scanning electron microscopy, goniometer, and universal testing machine. Curing results show that a 7-min to 25-min room temperature curing can be achieved, providing one possibility of shortening the surgery time. In vitro biodegradation test demonstrates that a certain proportion of the polyurethane film will be hydrolyzed in a foregone manner after a period of time (7 weeks). The adhesion strengths of these adhesives show a strong bonding between pieces of tissue, which makes them qualified for application in a moist environment.

Novel Tumor-Microenvironment-Based Sequential Catalytic Therapy by Fe(II)-Engineered Polydopamine Nanoparticles.

Traditional tumor treatments suffer from severe side effects on account of their invasive process and inefficient outcomes. Featuring a unique physical microenvironment, the tumor microenvironment (TME) provides a new research direction for designing more efficient and safer treatment paradigms. In this study, we fabricated a polydopamine (PDA)-based TME-responsive nanosystem, which successfully integrates glucose degradation, the Fenton reaction, and photothermal therapy for efficient cancer therapy. Through a convenient hydrothermal method, Fe2+-doped Fe(II)-PDA nanoparticles were successfully fabricated, which show an excellent photothermal effect and interesting reactivity for the Fenton reaction. Instead of introducing toxic anticancer agents, natural glucose oxidase (GOD) was grafted on Fe(II)-PDA, forming a cascade catalytic nanomedicine for a specific response to the glucose in TME. GOD grafted on Fe(II)-PDA-GOD is ought to catalyze abundant glucose in TME into gluconic acid and H2O2. The concomitant generation of H2O2 can enhance the efficiency of the sequential Fenton reaction, producing abundant hydroxyl radicals (•OH) for cancer therapy. Besides, the overconsumption of intratumoral glucose also could inhibit tumor growth by reducing the energy supply. Taken together, the in vitro and in vivo antitumor studies of such TME-based Fe(II)-PDA-GOD nanosystems displayed a favorable synergistic potency of glucose degradation, the Fenton reaction, and photothermal therapy against tumor growth. Our design expands the biological application of multifunctional PDA while providing novel strategies toward effective antitumor treatment with minimal side effects.

Enterovirus 71 VP1 promotes mouse Schwann cell autophagy via ER stress­mediated PMP22 upregulation.

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease­related deaths due to fatal neurological complications. EV71 structural viral protein 1 (VP1) promotes viral replication by inducing autophagy in neuron cells, but the effect of VP1 on myelin cells is unclear. The present study aimed to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells. An EV71 VP1­expressing vector (pEGFP­C3­VP1) was generated and transfected into mouse Schwann cells. Transmission electron microscopy and western blot analysis for microtubule­associated protein 1 light chain 3 α (LC3) II (an autophagy marker) were used to assess autophagy. Reverse transcription­quantitative PCR and immunofluorescence were performed to determine the expression of peripheral myelin protein 22 (PMP22). Small interfering RNA against PMP22 was used to investigate the role of PMP22 in mouse Schwann cell autophagy. Salubrinal [a selective endoplasmic reticulum (ER) stress inhibitor] was used to determine whether PMP22 expression was affected by ER stress. The present results indicated that VP1 promoted mouse Schwann cell autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3II and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by salubrinal. In conclusion, VP1 promoted mouse Schwann cell autophagy through upregulation of ER stress­mediated PMP22 expression. Therefore, the VP1/ER stress/PMP22 autophagy axis may be a potential therapeutic target for EV71 infection­induced fatal neuronal damage.

Improved lignocellulose-degrading performance during straw composting from diverse sources with actinomycetes inoculation by regulating the key enzyme activities.

This study was conducted to assess the effect of thermophilic actinomycetes inoculation on the lignocellulose degradation, enzyme activities and microbial community during different types of straw composting from wheat, rice, corn and soybean. The results showed that actinomycetes inoculation not only changed the structure of actinomycetic and bacterial community but also accelerated the degradation of cellulose, hemicellulose and lignin and increased the key enzymes activities including CMCase, Xylanase, manganese peroxidase, lignin peroxidase and laccase during composting particularly from wheat straw and rice straw. The key enzyme and physiochemical parameters which affected organic fractions degradation have been identified by redundancy analysis. The combined application of actinomycete inoculation and urea addition as a source of nitrogen was suggested to regulate the key enzyme activities and lignocellulose degradation, which lays a foundation for effectively managing organic wastes from different types of crop straws by composting.

Mortality in Children with Severe Hand, Foot and Mouth Disease in Guangxi, China.

OBJECTIVE: To analyze the clinical features of children with hand foot and mouth disease (HFMD) who died. METHODS: 331 deaths due to HFMD between 2010 and 2014 were included in this retrospective study; 15 autopsies were performed. RESULTS: Most deaths were seen in children aged below 3 y, and with enterovirus 71 infection (91%). The mean (SD) duration of HFMD from onset to death was 3.7(2.9) d. The mean (SD) age of fast progressors (from onset to death less than 4 days) was 17.4 (9.2) mo. Most of them were diagnosed as stage 3 and stage 4 of HFMD. Various pathological changes were observed in brain after autopsy, especially in brain stem and medulla. CONCLUSION: The brain stem encephalitis with the neurotropism of enteroviruses seems to be the main contributor to the death in HFMD.

Noninvasive monitoring of nanoparticle clearance and aggregation in blood circulation by in vivo flow cytometry.

Nanoparticles have been widely used in biomedical research as drug carriers or imaging agents for living animals. Blood circulation is crucial for the delivery of nanoparticles, which enter the bloodstream through injection, inhalation, or dermal exposure. However, the clearance kinetics of nanoparticles in blood circulation has been poorly studied, mainly because of the limitations of conventional detection methods, such as insufficient blood sample volumes or low spatial-temporal resolution. In addition, formation of nanoparticle aggregates is a key determinant for biocompatibility and drug delivery efficiency. Aggregation behavior of nanoparticles in blood is studied using dynamic light scattering in serum or serum protein solutions, which is still very different from in vivo condition. In this work, we monitored the dynamics of nanoparticle concentration and formation of nanoparticle aggregates in the bloodstream in live animals using in vivo flow cytometry (IVFC). The results indicated that nanoparticles in smaller size could stay longer in the bloodstream. Polyethylene glycol (PEG)-modification could prolong circulating time and reduce the formation of aggregates in the blood circulation. Our work shows that IVFC can be a powerful tool for pharmacokinetic studies of nanoparticles and other drug carriers, assessing cell-targeting efficiency, as well as potentially measuring cardiac output and hepatic function in vivo.

Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis.

The dissemination, seeding, and colonization of circulating tumor cells (CTCs) serve as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTCs in the (pre-)metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both a CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly(latic-co-glycolic acid) nanoparticles (NPs). The membrane-associated protein cocktails on neutrophils membrane were mostly translocated to the surface of NM-NP via a nondisruptive approach, and the biobinding activity of neutrophils was highly preserved. Compared with uncoated NP, NM-NP exhibited enhanced cellular association in 4T1 cell models under shear flow in vitro, much higher CTC-capture efficiency in vivo, and improved homing to the premetastatic niche. Following loading with carfilzomib, a second generation of proteasome inhibitor, the NM-NP-based nanoformulation (NM-NP-CFZ) selectively depleted CTCs in the blood, prevented early metastasis and potentially inhibited the progress of already-formed metastasis. Our NP design can neutralize CTCs in the circulation and inhibit the formation of a metastatic niche.