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.

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.

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.

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.

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.

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.].

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.

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.

Metformin inhibits hepatocellular carcinoma development by inducing apoptosis and pyroptosis through regulating FOXO3.

This study aimed to expand our understanding of metformin (Met) in inhibiting hepatocellular carcinoma (HCC) progression and to investigate its underlying mechanism. Met was administrated to HCC cells at 5, 10, and 20 µM, after which the cell phenotype was evaluated. RNA-seq cluster analysis was used to screen for target genes modulated by Met. Luciferase activity and ChIP assays were performed to detect the effect of FOXO3 on the transcriptional activation of NLRP3. We evaluated the effect of Met and FOXO3 and on the growth of HCC cells in vivo. Met inhibited HCC cell proliferation and promoted apoptosis. Met also induced pyroptosis of HCC cells. FOXO3 was significantly upregulated by Met treatment, and FOXO3 activated transcription of NLRP3. Cells after Met treatment together with FOXO3 knockdown have a stronger colony formation and migration ability but a lower apoptosis rate compared to the Met treatment alone group. In vivo, Met inhibited HCC tumor growth. The tumors in Met treatment and FOXO3 knockdown group grew faster than in Met treatment group. Thus, Met attenuates HCC cell development by inducing apoptosis and pyroptosis. This effect of metformin is partially dependent on FOXO3 which can activate the transcription of NLRP3.

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective.

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.

Tailoring Materials with Specific Wettability in Biomedical Engineering.

As a fundamental feature of solid surfaces, wettability is playing an increasingly important role in our daily life. Benefitting from the inspiration of biological paradigms and the development in manufacturing technology, numerous wettability materials with elaborately designed surface topology and chemical compositions have been fabricated. Based on these advances, wettability materials have found broad technological implications in various fields ranging from academy, industry, agriculture to biomedical engineering. Among them, the practical applications of wettability materials in biomedical-related fields are receiving remarkable researches during the past decades because of the increasing attention to healthcare. In this review, the research progress of materials with specific wettability is discussed. After briefly introducing the underlying mechanisms, the fabrication strategies of artificial materials with specific wettability are described. The emphasis is put on the application progress of wettability biomaterials in biomedical engineering. The prospects for the future trend of wettability materials are also presented.

Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications.

Therapeutic nanoparticles are designed to enhance efficacy, real-time monitoring, targeting accuracy, biocompatibility, biodegradability, safety, and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials. Recently, bio-inspired metal nanoclusters (NCs) consisting of several to roughly dozens of atoms (<2 nm) have attracted increasing research interest, owing to their ultrafine size, tunable fluorescent capability, good biocompatibility, variable metallic composition, and extensive surface bio-functionalization. Hybrid core-shell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules, such as proteins (enzymes, antigens, and antibodies), DNA, and specific cells, create fluorescently visualized molecular nanoparticle. The resultant nanoparticles possess combinatorial properties and synergistic efficacy, such as simplicity, active bio-responsiveness, improved applicability, and low cost, for combination therapy, such as accurate targeting, bioimaging, and enhanced therapeutic and biocatalytic effects. In contrast to larger nanoparticles, bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems. Notably, advances in nanoscience, interfacial chemistry, and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes. The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications, with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds. In the different hybrid platform, we summarize the current challenges and emerging perspectives, which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.

Protein-Based Hybrid Responsive Microparticles for Wound Healing.

The in-depth development of biological materials, especially natural polymer materials, has injected strong vitality into clinical wound treatment. Here, a new type of controllable responsive microparticles composed of several natural polymer materials was presented for drug release and wound healing. These hybrid microparticles consisted of silk fibroin, gelatin, agarose, and black phosphorus quantum dots (BPQDs) and were loaded with growth factors and antibacterial peptides. Under near-infrared (NIR) irradiation, BPQDs could absorb the NIR light and increase the temperature of the microparticles to the melting point of gelatin. When the gelatin started to melt, the encapsulated drugs were gradually released because of the reversible phase transformation. Both in vitro and in vivo experiments have demonstrated that the BPQD-laden microparticles with a NIR-responsive feature could achieve the desired controllable release of growth factors to promote neovascularization formation. In addition, because antibacterial peptides were also mixed with the secondary hydrogel and encapsulated in the scaffolds, the microparticles are imparted with the antibacterial ability during storage and usage. These characteristics of BPQD-laden natural protein hybrid microparticles make them ideal for drug delivery and wound healing.

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.

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.

Hierarchically Molecular Imprinted Porous Particles for Biomimetic Kidney Cleaning.

Blood purification by adsorption of excessive biomolecules is vital for maintaining human health. Here, inspired by kidney self-purification, which removes a number of biomolecules with different sizes simultaneously, hierarchical molecular-imprinted inverse opal particles integrated with a herringbone microfluidic chip for efficient biomolecules cleaning are presented. The particle possesses combinative porous structure with both surface and interior imprints for the specific recognition of small molecules and biomacromolecules. Additionally, the presence of the herringbone mixer largely improve the adsorption efficiency due to enhanced mixing. Moreover, the inverse opal framework of the particles give rise to optical sensing ability for self-reporting of the adsorption states. These features, together with its reusability, biosafety, and biocompatibility, make the platform highly promising for clinical blood purification and artificial kidney construction.

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.