Hydrogel Encapsulated Core-Shell Photonic Barcodes for Multiplex Biomarker Quantification.

Acute myocardial infarction (AMI) is one of the most fatal diseases in the world in recent decades. Because rapid and accurate determination of AMI has the potential to save millions of lives globally, the development of new diagnostic method is of great significance. Here, we designed a magnetic responsive structural color core-shell hydrogel microcarrier as a novel platform for a high-throughput detection of a variety of cardiovascular biomarkers. The composite hydrogel shell was formed from methacrylated gelatin, acrylic acid, and poly(ethylene glycol diacrylate), and the core silica photonic crystals acted as a detector. Fe3O4 nanoparticles were infused into the void of the core-shell structure to impart magnetic response properties to the encoded carrier. The findings indicated that our method possessed high sensitivity and reliable specificity in the high-throughput detection of AMI-related biomarkers Myo, cTnI, and BNP. In addition, the developed method not only showed good specificity and high sensitivity in clinical samples but also was comparable to the clinical gold standard method. Therefore, the magnetic response structural color core-shell hydrogel carriers were regarded as a potential approach to detect some AMI disease-related biomarkers.

Self-Propelled Structural Color Cylindrical Micromotors for Heavy Metal Ions Adsorption and Screening.

Water contamination resulting from heavy metal ions (HMIs) poses a severe threat to public health and the ecosystem. Attempts are tending to develop functional materials to realize efficient and intelligent adsorption of HMIs. Herein, self-propelled structural color cylindrical micromotors (SCCMs) with reversible HMIs adsorption capacity and self-reporting property are presented. The SCCMs are fabricated by using platinum nanoparticles (Pt NPs) tagged responsive hydrogel of carboxymethyl chitosan (CMC) and polyacrylamide (PAM) to asymmetrically replicate tubular colloidal crystal templates (TCCTs). Owing to the self-propelled motion of the SCCMs, the enhancive ion-motor interactions bring significantly improved decontamination efficiency. Moreover, it is demonstrated that the SCCMs can realize quick and naked-eye-visible self-reporting during the adsorption/desorption process based on their responsive structure color variation and superior adsorption capacity. Thus, it is anticipated that such intelligent SCCMs can significantly facilitate the evolution of sensing assays and diverse environmental fields.

Tailoring conductive inverse opal films with anisotropic elliptical porous patterns for nerve cell orientation.

BACKGROUND: The nervous system is critical to the operation of various organs and systems, while novel methods with designable neural induction remain to exploit. RESULTS: Here, we present a conductive inverse opal film with anisotropic elliptical porous patterns for nerve orientation induction. The films are fabricated based on polystyrene (PS) inverse opal scaffolds with periodical elliptical porous structure and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) mixed polyacrylamide (PAAm) polymers fillers. It is demonstrated that the anisotropic elliptical surface topography allows the nerve cells to be induced into orientation connected with the stretching direction. Because of the anisotropic features of the film which can be stretched into different directions, nerve cells can be induced to grow in one or two directions, forming a neural network and promoting the connection of nerve cells. It is worth mentioning that the PEDOT:PSS-doped PAAm hydrogels endow the film with conductive properties, which makes the composite films be a suitable candidate for neurites growth and differentiation. CONCLUSIONS: All these features of the conductive and anisotropic inverse opal films imply their great prospects in biomedical applications.

Label-Free Quantifications of Multiplexed Mycotoxins by G-Quadruplex Based on Photonic Barcodes.

Multiplexed quantification of mycotoxins is of great significance in food safety. Here, novel photonic crystal (PhC) barcodes with G-quadruplex aptamer encapsulated for label-free multiplex mycotoxins quantification are developed. The probes are immobilized on PhC barcodes to form a molecular beacon (MB), which contains the sequences of mycotoxin aptamers and a G-quadruplex. In the presence of the target, the hairpin structure of MB would open and the region of the G-quadruplex is exposed, which subsequently combines with Thioflavin T (ThT) to produce fluorescence. The relative fluorescence intensity increased as the mycotoxins concentration increased in a linear range from 1.0 pg/mL to 100 ng/mL. Moreover, the multiplexed mycotoxins quantification could be achieved by tuning the structural color of the PhC barcodes. We demonstrate that this method with high accuracy and specificity for multiplexed detection of mycotoxins, with the sensitivity of the detection as low as 0.70 pg/mL. Our results show that G-quadruplex-encapsulated PhC barcodes offer a novel simple and label-free pathway toward the multiplex screen assay of mycotoxins for food safety.

Distance-based quantification of miRNA-21 by the coffee-ring effect using paper devices.

Enabled by the coffee-ring effect, a paper-based signal transduce method is employed for catalytic hairpin assembly (CHA) amplification and hybridization chain reaction (HCR) to achieve miRNA quantification. Once the target miRNAs appeared, it was circularly used by CHA to initiate HCR amplification to produce a large number of G-quadruplex, which is combined with hemin to form a hemin/G-quadruplex DNAzyme. The DNAzyme catalyzes a colorimetric reaction to produce colored nanoparticles, which were converted to the end edge of the paper by evaporation-driven flow, forming a visible colored band. Higher concentration of miRNA led to more colored nanoparticles and thus a longer colored band that can simply be measured by a ruler. The results of determination of miRNA in samples demonstrate that the relative standard deviation of the proposed approach is 5.2%, highly sensitive and repeatable, with a working range 1.0 to 1000 pM and a LOD of 0.2 pM. The paper-based analytical device as a novel platform offers a new signal transduce pathway toward the detection of low-abundance biomarkers for diagnosis.Graphical abstract Schematic representation of the principle for quantification of miRNA on paper based on the coffee-ring effect.

Visualized Quantitation of Trace Nucleic Acids Based on the Coffee-Ring Effect on Colloid-Crystal Substrates.

We report a visualized quantitative detection method for nucleic acid amplification tests based on the coffee-ring effect on colloid-crystal substrates. The solution for loop-mediated isothermal amplification (LAMP) of DNA is drop cast on a colloid-crystal surface. After complete drying, a coffee ring containing the LAMP byproduct (i.e., magnesium pyrophosphate) is formed, and it is found that the width of the coffee ring is linearly correlated to the logarithm of the original DNA concentration before the isothermal amplification. Importantly, compared with other substrates, we found that the colloid-crystal substrate is an appropriate substrate for carrying out the assay of high sensitivity. On the basis of these findings, we develop a coffee-ring-based assay for quantitative readout of trace DNA in a sample. The assay requires 0.50 µL of the sample and is completed in 5 min in a homemade chamber with constant humidity. Semiquantitative detection of trace DNA is performed using naked eyes. With the use of a smartphone, the DNA in a sample can be quantitatively detected with a limit of detection of 20 copies.

Bio-inspired photonic crystals for naked eye quantification of nucleic acids.

Herein, a chip imitating the desert beetle shell was presented for naked eye nucleic acid quantification. The hydrophobic photonic crystal substrate treated by ultraviolet local irradiation could effectively disperse the sample into hundreds of droplets for digital loop-mediated isothermal amplification (dLAMP). Pyrophosphate (PPI), a by-product of the LAMP reaction, combined with magnesium ions to form a poorly soluble precipitate. It could be fixed on a silica substrate due to complexation, resulting in the disappearance of the structural color of the photonic crystals. The number of points without structural color contains the information of the copy number of nucleic acids in the sample. This chip could achieve the naked eye quantitative detection of Salmonella DNA without fluorescence or other chromogenic reagents. Thus, the chip designed in this study can help the development of digital nucleic acid detection under limited resource settings (LRS) and can be suitable for POCT (point of care test) standards.

Toward Quantitative Chemical Analysis Using a Ruler on Paper: An Approach to Transduce Color to Length Based on Coffee-Ring Effect.

We report a quantitative analytical method using the naked eye. The method is based on the coffee-ring effect on paper, which converts a colored solution to stains on the paper. It is found that the width of the colored stains is correlated to the concentration of analyte so that quantitative analysis can be accomplished using a ruler. The influence of the shape and lamination of the paper reservoir to the test results is studied to find the optimal one for unambiguous analysis. It is also found that the sample color does not cause interference to the test. The applicability of the method to quantitative chemical analysis is demonstrated by detection of glucose and lactate.

Grass carp (Ctenopharyngodon idellus) invariant chain of the MHC class II chaperone protein associates with the class I molecule.

The invariant chain (Ii) is an important immune molecule, as it assists major histocompatibility complex (MHC) class II molecules to present antigenic peptides. The relationship between the Ii and MHC molecules in teleosts remains poorly understood. This study focused on the molecular structure of grass carp Ii (gIi), its organ distribution, correlations with gene transcription, and the association with MHC. gIi cDNA was cloned using designed degenerate primers and the rapid amplification of cDNA ends method (RACE). The gIi sequence was 92%-96% similar to that of other teleosts, but only 52%-67% similar to that of mammals, respectively. The gIi gene was distributed in all 12 organs examined by PCR. The gIi gene transcription levels were markedly higher in organs enriched with immune cells than in other organs (P < 0.01). Moreover, positive correlations were detected between transcription levels of the gIi and gMhcI or II genes in different organs (r = 8.415-8.523, P = 0.001). The gIi co-localized on endomembrane systems with either class I or II molecules in co-transfected cells observed by a laser confocal. Further testing confirmed that the gIi bound gMHCI and II molecules. Taken together, these results indicate that the gIi is associated with MHC class I and II molecules, suggesting homology of both MHC molecules.

Procalcitonin Detection Using Immunomagnetic Beads-Mediated Surface-Enhanced Raman Spectroscopy.

The early detection of procalcitonin (PCT) is crucial for diagnosing bacterial infections due to its high sensitivity and specificity. While colloidal gold colorimetric and immune-chemiluminescence methods are commonly employed in clinical detection, the former lacks sensitivity, and the latter faces challenges with a brief luminescence process and an elevated background. Here, we introduce a novel approach for the quantitative analysis of PCT using surface-enhanced Raman spectroscopy (SERS), leveraging the enhanced properties of metal nanoparticles. Simultaneously, we employed a magnetic nanoparticle coating and surface biofunctionalization modification to immobilize PCT-trapping antibodies, creating the required immune substrates. The resulting magnetic nanoparticles and antibody complexes, acting as carriers and recognition units, exhibited superparamagnetism and the specific recognition of biomarkers. Then, this complex efficiently underwent magnetic separation with an applied magnetic field, streamlining the cumbersome steps of traditional ELISA and significantly reducing the detection time. In conclusion, the exploration of immunomagnetic bead detection technology based on surface-enhanced Raman spectroscopy holds crucial practical significance for the sensitive detection of PCT.

Emerging platelet-based drug delivery systems.

Drug delivery systems are becoming increasingly utilized; however, a major challenge in this field is the insufficient target of tissues or cells. Although efforts with engineered nanoparticles have shown some success, issues with targeting, toxicity and immunogenicity persist. Conversely, living cells can be used as drug-delivery vehicles because they typically have innate targeting mechanisms and minimal adverse effects. As active participants in hemostasis, inflammation, and tumors, platelets have shown great potential in drug delivery. This review highlights platelet-based drug delivery systems, including platelet membrane engineering, platelet membrane coating, platelet cytoplasmic drug loading, genetic engineering, and synthetic/artificial platelets for different applications.

Carbon nanotubes integrated photonic barcodes in Herringbone Microfluidics for Multiplex Biomarker Quantification.

Early monitoring of cardiovascular disease (CVD) is crucial for its treatment and prognosis. Hence, highly specific and sensitive detection method is urgently needed. In this study, we propose a novel herringbone microfluid chip with aptamer functionalized core-shell photonic crystal (PhC) barcode integration for high throughput multiplex CVD detection. Based on the PhC derived from co-assembled carboxylated single-wall carbon nanotubes and silicon dioxide nanoparticles, we obtain core-shell PhC barcodes by hydrogel replicating and partially etching. These core-shell PhC barcodes not only retain the original structural colors coding element, but also fully expose a large number of carboxyl elements in the ore for the probe immobilization. We further combine the functionalized barcodes with herringbone groove microfluidic chip to elucidate its acceptability in testing clinical sample. It is demonstrated that the special design of microfluidic chip can significantly enhance fluid vortex resistance and contact frequency, improving the sample capture efficiency and detection sensitivity. These features indicate that our core-shell PhC barcodes-integrated herringbone microfluidic system possesses great potential for multiplex biomarker detection in clinical application.

Biomimetic liposomes hybrid with erythrocyte membrane modulate dendritic cells to ameliorate systemic lupus erythematosus.

Dendritic cells (DCs)-based immunotherapy has shown immense promise in systemic lupus erythematosus (SLE) treatment. However, existing carrier strategies such as polymers, liposomes, and polypeptides, are difficult to achieve active targeting to DCs due to their intricate interaction with biological systems. Since DCs represent a class of phagocytes responsible for the removal of senescent or damaged erythrocytes, we hypothesize that hybrid vesicles containing erythrocytes membrane components could be presented to be potent drug carriers to target DCs specifically. Herein, inspired by the cell membrane fusion technique, we develop hybrid biomimetic liposomes (R-Lipo) by fusing natural erythrocyte membrane vesicles and artificial liposomes for DCs-targeted SLE therapy. The resultant R-Lipo exhibited excellent biocompatibility and was shown to be effectively internalized by DCs both in vitro and in vivo. Using an immunosuppressant, mycophenolic acid (MPA), as the model drug, MPA-loaded R-Lipo powerfully suppressed DCs maturation and efficiently controlled the duration of lupus nephritis without apparent side effects. Our findings provide a safe, effective, and easy-to-prepare biomimetic vesicle platform for the treatment of SLE and other DC-associated diseases.

Role of adenosine A2a receptor in cancers and autoimmune diseases.

Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.

3D-printed fish gelatin scaffolds for cartilage tissue engineering.

Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging, trauma, and obesity, and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging. Here, we present a three-dimensional (3D) printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration. To make the scaffold, cold-water fish skin gelatin was combined with sodium alginate to increase viscosity, printability, and mechanical strength, and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology. Then, the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further. These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere, proliferate, and communicate with each other, transport nutrients, and prevent further damage to the joint. More importantly, we found that cold-water fish gelatin scaffolds were nonimmunogenic, nontoxic, and biodegradable. We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model. Thus, cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.

Correction: A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.

[This corrects the article DOI: 10.1039/D0RA09106E.].

Structural Color Medical Patch with Surface Dual-Properties of Wet Bioadhesion and Slipperiness.

Developing a self-reporting bioadhesive patch that has strong adhesion to the wet tissues and meanwhile can avoid adhering to the adjacent tissues is a current research difficulty and challenge. In this paper, inspired by the wet adhesion of spider web, slippery surface of Nepenthes, and structural color phenomena of chameleons, a novel structural color medical patch with surface dual-properties of wet bioadhesion and slipperiness for internal tissue repair based on inverse opal scaffold is presented. The adhesive surface made by poly(acrylic acid)-polyethylene glycol-N-hydroxysuccinimide ester and gelatin hydrogel can attain tough adhesion to internal wet tissues by absorbing tissue interfacial water and the covalent cross-linking between the hydrogel and tissue. Besides, the slippery surface made by liquid paraffin infused inverse opal scaffold can avoid adhesion to the adjacent tissues. It is demonstrated that the designed patch can adhere tightly to the defect tissue and improve the tissue repair without adjacent adhesion when applied in a rat model with full-thickness perforation of the stomach wall. In addition, the responsive structural color can supply a color-sensing monitoring to evaluate the adhesive and repair process. These features impart the bioinspired patch with great scientific significance and broad clinical application prospects.

A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.

Wound healing is a ubiquitous healthcare problem in clinical wound management. In this paper, the fabrication of a graphene hybrid supramolecular hydrogel (GS hydrogel) for wound dressing applications is demonstrated. The hydrogel is composed of two components, including N-acryloyl glycinamide (NAGA) as the scaffold and graphene as the photothermally responsive active site for photothermal therapy. Based on the multiple hydrogen bonds between the dual amide motifs in the side chain of N-acryloyl glycinamide, the hydrogel exhibits high tensile strength (≈1.7 MPa), good stretchability (≈400%) and self-recoverability. In addition, the GS hydrogel shows excellent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), benefiting from the addition of graphene that possesses great photothermal transition activity (≈85%). Significantly, in vivo animal experiments also demonstrated that the GS hydrogel effectively accelerates the wound healing processes by eradicating microbes, promoting collagen deposition and angiogenesis. In summary, this GS hydrogel demonstrates excellent mechanical performance, photothermal antimicrobial activity, and promotes skin tissue regeneration, and so has great application potential as a promising wound dressing material in clinical use.

Morphological Hydrogel Microfibers with MXene Encapsulation for Electronic Skin.

Electronic skins with distinctive features have attracted remarkable attention from researchers because of their promising applications in flexible electronics. Here, we present novel morphologically conductive hydrogel microfibers with MXene encapsulation by using a multi-injection coflow glass capillary microfluidic chip. The coaxial flows in microchannels together with fast gelation between alginate and calcium ions ensure the formation of hollow straight as well as helical microfibers and guarantee the in situ encapsulation of MXene. The resultant hollow straight and helical MXene hydrogel microfibers were with highly controllable morphologies and package features. Benefiting from the easy manipulation of the microfluidics, the structure compositions and the sizes of MXene hydrogel microfibers could be easily tailored by varying different flow rates. It was demonstrated that these morphologically conductive MXene hydrogel microfibers were with outstanding capabilities of sensitive responses to motion and photothermal stimulations, according to their corresponding resistance changes. Thus, we believe that our morphologically conductive MXene hydrogel microfibers with these excellent features will find important applications in smart flexible electronics especially electronic skins.

Responsive Janus Structural Color Hydrogel Micromotors for Label-Free Multiplex Assays.

Micromotors with self-propelling ability demonstrate great values in highly sensitive analysis. Developing novel micromotors to achieve label-free multiplex assay is particularly intriguing in terms of detection efficiency. Herein, structural color micromotors (SCMs) were developed and employed for this purpose. The SCMs were derived from phase separation of droplet templates and exhibited a Janus structure with two distinct sections, including one with structural colors and the other providing catalytic self-propelling functions. Besides, the SCMs were functionalized with ion-responsive aptamers, through which the interaction between the ions and aptamers resulted in the shift of the intrinsic color of the SCMs. It was demonstrated that the SCMs could realize multiplex label-free detection of ions based on their optical coding capacity and responsive behaviors. Moreover, the detection sensitivity was greatly improved benefiting from the autonomous motion of the SCMs which enhanced the ion-aptamer interactions. We anticipate that the SCMs can significantly promote the development of multiplex assay and biomedical fields.