Hepatocellular carcinoma biomarkers screening based on hydrogel photonic barcodes with tyramine deposition amplified ELISA.

Hepatocellular carcinoma (HCC), as one of the most lethal cancers, significantly impacts human health. Attempts in this area tends to develop novel technologies with sensitive and multiplexed detection properties for early diagnosis. Here, we present novel hydrogel photonic crystal (PhC) barcodes with tyramine deposition amplified enzyme-linked immunosorbent assay (ELISA) for highly sensitive and multiplexed HCC biomarker screening. Because of the abundant amino groups of acrylic acid (AA) component, the constructed hydrogel PhC barcodes with inverse opal structure could facilitate the loading of antibody probes for subsequent detection of tumor markers. By integrating tyramine deposition amplified ELISA on the barcode, the detection signal of tumor markers has been enhanced. Based on these features, it is demonstrated that the hydrogel PhC barcodes with tyramine deposition amplified ELISA could realize highly sensitive and multiplexed detection of HCC-related biomarkers. It was found that this method is flexible, sensitive and accurate, suitable for multivariate analysis of low abundance tumor markers and future cancer diagnosis. These features make the newly developed PhC barcodes an innovation platform, which possesses tremendous potential for practical application of low abundance targets.

Biomimetic Anticoagulated Porous Particles with Self-Reporting Structural Colors.

Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood-related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric "fingerprint" for each target can be obtained and summarized as a database. Besides, a portable test-strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors-derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis.

Sprayable Multifunctional Black Phosphorus Hydrogel with On-Demand Removability for Joint Skin Wound Healing.

Wound healing remains a critical challenge in regenerative engineering. Great efforts are devoted to develop functional patches for wound healing. Herein, a novel sprayable black phosphorus (BP)-based multifunctional hydrogel with on-demand removability is presented as a joints' skin wound dressing. The hydrogel is facilely prepared by mixing dopamine-modified oxidized hyaluronic acid, cyanoacetategroup-functionalized dextran containing black phosphorus, and the catalyst histidine. The catechol-containing dopamine can not only enhance tissue adhesiveness, but also endow the hydrogel with antioxidant capacity. In addition, benefiting from the photothermal conversion ability of the BP and thermally reversible performance of the formed C═C double bonds between aldehyde groups and cyanoacetate groups, the resulting hydrogel displays excellent antibacterial performance and on-demand dissolving ability under NIR irradiation. Moreover, by loading vascular endothelial growth factor into the hydrogel, the promoted migration and angiogenesis effects of endothelial cells can also be achieved. Based on these features, it is demonstrated that such sprayable BP hydrogels can effectively facilitate joint wounds healing by accelerating angiogenesis, alleviating inflammation, and improving wound microenvironment. Thus, it is believed that this NIR-responsive removable BP hydrogel dressing will put forward an innovative concept in designing wound dressings.

Tailoring biomaterials for biomimetic organs-on-chips.

Organs-on-chips are microengineered microfluidic living cell culture devices with continuously perfused chambers penetrating to cells. By mimicking the biological features of the multicellular constructions, interactions among organs, vascular perfusion, physicochemical microenvironments, and so on, these devices are imparted with some key pathophysiological function levels of living organs that are difficult to be achieved in conventional 2D or 3D culture systems. In this technology, biomaterials are extremely important because they affect the microstructures and functionalities of the organ cells and the development of the organs-on-chip functions. Thus, herein, we provide an overview on the advances of biomaterials for the construction of organs-on-chips. After introducing the general components, structures, and fabrication techniques of the biomaterials, we focus on the studies of the functions and applications of these biomaterials in the organs-on-chips systems. Applications of the biomaterial-based organs-on-chips as alternative animal models for pharmaceutical, chemical, and environmental tests are described and highlighted. The prospects for exciting future directions and the challenges of biomaterials for realizing the further functionalization of organs-on-chips are also presented.

Bioinspired optical and electrical dual-responsive heart-on-a-chip for hormone testing.

Heart-on-chips have emerged as a powerful tool to promote the paradigm innovation in cardiac pathological research and drug development. Attempts are focused on improving microphysiological visuals, enhancing bionic characteristics, as well as expanding their biomedical applications. Herein, inspired by the bright feathers of peacock, we present a novel optical and electrical dual-responsive heart-on-a-chip based on cardiomyocytes hybrid bright MXene structural color hydrogels for hormone toxicity evaluation. Such hydrogels with inverse opal nanostructure are generated by using pregel to replicate MXene-decorated colloidal photonic crystal (PhC) array templates. The attendant MXene in the hydrogels could not only enhance the saturation of structural color, but also ensure the composite hydrogel with excellent electroconductivity to facilitate the synergetic beating of their surface cultured cardiomyocytes. In this case, the hydrogels would undergo a synchronous deformation and generate shift in corresponding photonic band gap and structural color, which could be employed as visual signal for self-reporting of the cardiomyocyte mechanics. Based on these features, we demonstrated the practical value of the optical and electrical dual-responsive structural color MXene hydrogels constructed heart-on-a-chip in hormone toxicity testing. These results indicated that the proposed heart-on-a-chip might find broad prospects in drug screening, biological research, and so on.

Erythrocyte-Inspired Functional Materials for Biomedical Applications.

Erythrocytes are the most abundant cells in the blood. As the results of long-term natural selection, their specific biconcave discoid morphology and cellular composition are responsible for gaining excellent biological performance. Inspired by the intrinsic features of erythrocytes, various artificial biomaterials emerge and find broad prospects in biomedical applications such as therapeutic delivery, bioimaging, and tissue engineering. Here, a comprehensive review from the fabrication to the applications of erythrocyte-inspired functional materials is given. After summarizing the biomaterials mimicking the biological functions of erythrocytes, the synthesis strategies of particles with erythrocyte-inspired morphologies are presented. The emphasis is on practical biomedical applications of these bioinspired functional materials. The perspectives for the future possibilities of the advanced erythrocyte-inspired biomaterials are also discussed. It is hoped that the summary of existing studies can inspire researchers to develop novel biomaterials; thus, accelerating the progress of these biomaterials toward clinical biomedical applications.

Pollen-Inspired Photonic Barcodes with Prickly Surface for Multiplex Exosome Capturing and Screening.

Exosomes, which play an important role in intercellular communication, are closely related to the pathogenesis of disease. However, their effective capture and multiplex screening are still challenging. Here, inspired by the unique structure of pollens, we present novel photonic crystal (PhC) barcodes with prickly surface by hydrothermal synthesis for multiplex exosome capturing and screening. These pollen-inspired PhC barcodes are imparted with extremely high specific surface area and excellent prickly surface nanostructures, which can improve the capture rate and detection sensitivity of exosomes. As the internal periodic structures are kept during the hydrothermal synthesis process, the pollen-inspired PhC barcodes exhibit obvious and stable structural colors for identification, which enables multiplex detection of exosomes. Thus, the pollen-inspired PhC barcodes can not only effectively capture and enrich cancer-related exosomes but also support multiplex screening of exosomes with high sensitivity. These features make the prickly PhC barcodes ideal for the analysis of exosomes in medical diagnosis.

Aptamer-Functionalized Barcodes in Herringbone Microfluidics for Multiple Detection of Exosomes.

Tumor-derived exosomes are vital for clinical dynamic and accurate tumor diagnosis, thus developing sensitive and multiple exosomes detection technology has attracted remarkable attention of scientists. Here, a novel herringbone microfluidic device with aptamer-functionalized barcodes integration for specific capture and multiple detection of tumor-derived exosomes is presented. The barcodes with core-shell constructions are obtained by partially replicating the periodically ordered hexagonal close-packaged colloidal crystal beads. As their inverse opal hydrogel shell possesses rich interconnected pores, the barcodes could provide abundant surface area for functionalization of DNA aptamers to realize specific recognition of target exosomes. Besides, the encoded structure colors of the barcodes can be maintained stably during the detection events as their hardish cores are with sufficient mechanical strength. It is demonstrated that by embedding these barcodes in herringbone groove microfluidic device with designed patterns, the specific capture efficiency and synergetic detection of multiple tumor-derived exosomes in peripheral blood can be significantly improved due to enhanced resistance of turbulent flow. These features make the aptamer-functionalized barcodes and herringbone microfluidics integrated platform promising for exosomes extraction and dynamic tumor diagnosis.

Bioinspired Perovskite Nanocrystals-Integrated Photonic Crystal Microsphere Arrays for Information Security.

Information security occupies an important position in the era of big data. Attempts to improve the security performance tend to impart them with more additional encryption strategies. Herein, inspired by the wettability feature of Stenocara beetle elytra and signal model of traffic light, a novel array of perovskite nanocrystals (PNs)-integrated PhC microsphere for information security is presented. The photoluminescent PNs are encapsulated in angle-independent PhC microspheres to impart them with binary optical signals as coding information. Through the multimask superposition approach, PNs-integrated PhC microspheres with different codes are placed into fluorosilane-treated PDMS substrate to form different arrays. These arrays could converge moisture on PhC microspheres in wet environment, which avoids the ions loss of the PNs and effectively prevented mutual contamination. In addition, the fluorescence of the PNs inside PhC microspheres could reversibly quench or recover in response to the environmental moisture. Based on these features, it is demonstrated that the PNs-integrated PhC microsphere arrays could realize various information encryption modes, which indicate their excellent values in information security fields.

Self-Bonded Hydrogel Inverse Opal Particles as Sprayed Flexible Patch for Wound Healing.

Wound healing is an important issue for regenerative medicine. Attempts in this area tend to develop functional wound patches to promote the healing. Here, we present self-bonded hydrogel inverse opal particles as sprayed flexible patch for wound healing. Such particles were fabricated by infusing drugs-loaded gelatin (GT) and carrageenan (CG) pregel into inverse opal scaffolds, which were composed of biocompatible hyaluronic acid methacryloyl (HAMA) and gelatin methacryloyl (GelMA) with graphene oxide quantum dots (GO QDs) doping. Due to the photothermal conversion capability of GO QDs and temperature reversible phase-changing performance of GT/CG, the hybrid particles could undergo GT/CG liquid transformation under the near-infrared (NIR) irradiation, which made them adhere to each other and finally form a flexible patch. Following by the phase-change of GT/CG hydrogel, the encapsulated drugs were also controllably released from the inverse opal scaffold. As the inverse opal scaffolds of the hybrid particles were maintained, their drug release induced refractive index changes could be detected as visual structural color shifting, which could be utilized to monitor their delivery processes. Based on these features, we have demonstrated that the self-bonded particles, administered in the form of spray, could be applied for wound tissue healing and drug delivery monitoring. These results indicate that the self-bonded hydrogel particles have potential value as a multifunctional patch for clinical applications.

Ice-Inspired Lubricated Drug Delivery Particles from Microfluidic Electrospray for Osteoarthritis Treatment.

Particle-based drug delivery systems have a demonstrated value in osteoarthritis treatment. Research in this area trends to developing functional particles to improve the therapeutic effects. Herein, inspired by the super lubricated surface of ice that consists of a contiguous and ultrathin layer of bound water, we developed a 2-methylacryloyloxyethyl phosphorylcholine (MPC) decorated methacrylate anhydride- hyaluronic acid (HAMA) drug delivery particle with satisfying strength and enhanced lubrication from microfluidic electrospray for osteoarthritis treatment. Benefiting from the precise control of microfluidic electrospray flows, the generated drug delivery particles are imparted with well-tailored sizes and good dispersion. As the generated HAMA particles were modified by MPC with the positively (N+(CH3)3) and negatively (PO4-) charged chemical groups, they were imparted with enhanced lubrication effect and reduced friction on the joint interface by forming a hydrated lubricating layer. We have demonstrated that the MPC-modified HAMA particles could be employed as microcarriers for loading diclofenac sodium (DS) to inhibit the inflammatory response, thus further enhancing the osteoarthritis therapeutic effect in vivo and in vitro. Thus, the proposed drug delivery particles with satisfactory biocompatibility and therapeutic effect are great potential for clinical applications.

MXene-Integrated Microneedle Patches with Innate Molecule Encapsulation for Wound Healing.

Wound healing is a complex physiological process that involves coordinated phases such as inflammation and neovascularization. Attempts to promote the healing process tend to construct an effective delivery system based on different drugs and materials. In this paper, we propose novel MXene-integrated microneedle patches with adenosine encapsulation for wound healing. Owing to the dynamic covalent bonding capacity of boronate molecules with adenosine, 3-(acrylamido)phenylboronic acid- (PBA-) integrated polyethylene glycol diacrylate (PEGDA) hydrogel is utilized as the host material of microneedle patches. Benefitting from photothermal conversion capacity of MXene, the release of loaded adenosine could be accelerated under NIR irradiation for maintaining the activation signal around injury site. In vitro cell experiments proved the effect of MXene-integrated microneedle patches with adenosine encapsulation in enhancing angiogenesis. When applied for treating animal models, it is demonstrated that the microneedle patches efficiently promote angiogenesis, which is conductive to wound healing. These features make the proposed microneedle patch potential for finding applications in wound healing and other biomedical fields.

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.

Bioinspired MXene-integrated colloidal crystal arrays for multichannel bioinformation coding.

Information coding strategies are becoming increasingly crucial due to the storage demand brought by the information explosion. In particular, bioinformation coding has attracted great attention for its advantages of excellent storage capacity and long lifetime. Herein, we present an innovative bioinspired MXene-integrated photonic crystal (PhC) array for multichannel bioinformation coding. PhC arrays with similar structure to Stenocara beetle's back are utilized as the substrate, exhibiting properties of high throughput and stability. MXene nanosheets are further integrated on the PhC array's substrate with the assistance of the adhesion capacity of mussel-inspired dopamine (DA). Benefitting from their fluorescence resonance energy transfer effect, MXene nanosheets can quench the fluorescence signals of quantum dot (QD) modified DNA probes unless the corresponding targets exist. Additionally, these black MXene nanosheets can enhance the contrast of structural color. In this case, the encrypted information can be easily read out by simply observing the fluorescence signal of DNA probes. It is demonstrated that this strategy based on bioinspired MXene-integrated PhC arrays can realize high-throughput information encoding and encryption, which opens a chapter of bioinformation coding.

Advances of droplet-based microfluidics in drug discovery.

INTRODUCTION: Drug discovery through a large number of candidates with nearly unlimited possibilities is laborious, time-consuming, and incurs massive costs. It thus calls for fast and robust methods that allow for handling small amounts of reagents, automation, and high-throughput analysis. In this regard, droplet-based microfluidic platforms provide several unique advantages. Highly monodispersed droplets can be generated in a high frequency and serve as microcontainers with just a few femtoliter to nanoliter volume. Furthermore, each of them can be manipulated to initiate specific reactions in parallel. Consequently, droplet microfluidics is emerging as a useful tool for drug discovery and development. AREAS COVERED: The authors provide a brief overview of the latest developments of droplet-based microfluidic techniques for drug discovery and emphasize their applications at different stages, covering target selection, drug candidate identification, and preclinical research. EXPERT OPINION: Droplet-based microfluidics holds great potential in drug discovery due to its capability of reaction miniaturization and high-throughput analysis. However, its commercial applications are still at an early stage as the experiments are mostly implemented utilizing custom-built instruments in laboratory environments. Thus, joint efforts from scientists and engineers with multidisciplinary backgrounds are required to optimize the standardization and stability of droplet-based microfluidic platforms.

Biohybrid robotics with living cell actuation.

As simulators of organisms in Nature, soft robots have been developed over the past few decades. In particular, biohybrid robots constructed by integrating living cells with soft materials demonstrate the unique advantage of simulating the construction and functions of human tissues or organs, thus attracting extensive attention and research interest. Here, we present up-to-date studies concerning biohybrid robots with various biological actuators such as contractile cells and microorganisms. After presenting the basic components including biological components and synthetic materials, the controlling methods and locomotion modalities of biohybrid robots are clarified and summarized. We then focus on the applications, especially the biomedical applications, of the biohybrid robots including drug delivery, bioimaging, and tissue engineering. The challenges and prospects for the future development of biohybrid robots are also presented.

Multiplexed Detection Strategy for Bladder Cancer MicroRNAs Based on Photonic Crystal Barcodes.

Bladder cancer is a complex and highly prevalent disease associated with substantial morbidity and mortality rates. Detection and surveillance of biomarkers for bladder cancer are particularly critical in clinical diagnosis and prognostic monitoring. The current detection methods are limited to low sensitivity, low throughput, and high operational cost. In this paper, we present a multiplexed detection strategy for microRNA (miRNA) related to bladder cancer by utilizing photonic crystal (PhC) barcodes. PhC barcodes have characteristic reflective peaks generated by periodic orderly porous nanostructures, providing an ideal choice for encoding element. Besides, owing to the larger surface area provided by the structure, PhC barcodes is an effective platform for probes ligation and miRNAs detection. Compared with the planar microarrays, PhC barcodes avoid the problem of steric hindrance, making it express more efficient reaction and higher detection sensitivity. By introducing hybridization chain reaction (HCR), the detection efficiency of this strategy is greatly improved, making the rapid, accurate, high sensitivity quantification of miRNAs possible. The results indicated that the multiplexed detection strategy based on PhC barcodes can be applied to the clinical analysis of tumor markers.

Bioinspired programmable wettability arrays for droplets manipulation.

The manipulation of liquid droplets demonstrates great importance in various areas from laboratory research to our daily life. Here, inspired by the unique microstructure of plant stomata, we present a surface with programmable wettability arrays for droplets manipulation. The substrate film of this surface is constructed by using a coaxial capillary microfluidics to emulsify and pack graphene oxide (GO) hybrid N-isopropylacrylamide (NIPAM) hydrogel solution into silica nanoparticles-dispersed ethoxylated trimethylolpropane triacrylate (ETPTA) phase. Because of the distribution of the silica nanoparticles on the ETPTA interface, the outer surface of the film could achieve favorable hydrophobic property under selective fluorosilane decoration. Owing to the outstanding photothermal energy transformation property of the GO, the encapsulated hydrophilic hydrogel arrays could shrink back into the holes to expose their hydrophobic surface with near-infrared (NIR) irradiation; this imparts the composite film with remotely switchable surface droplet adhesion status. Based on this phenomenon, we have demonstrated controllable droplet sliding on programmable wettability pathways, together with effective droplet transfer for printing with mask integration, which remains difficult to realize by existing techniques.

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.

Stomatocyte structural color-barcode micromotors for multiplex assays.

Artificial micromotors have a demonstrated value in the biomedical area. Attempts to develop this technology tend to impart micromotors with novel functions to improve the values. Herein, we present novel structural color-barcode micromotors for the multiplex assays. We found that, by rapidly extracting solvent and assembling monodispersed nanoparticles in droplets, it could form stomatocyte colloidal crystal clusters, which not only showed striking structural colors and characteristic reflection peaks due to their ordered nanoparticles arrangement, but also provided effective cavities for the integration of functional elements. Thus, the micromotors with catalysts or magnetic elements in their cavities, as well as with the corresponding structural color coding, could be achieved by using the platinum and ferric oxide dispersed pre-gel to fill and duplicate the stomatocyte colloidal crystal clusters. We have demonstrated that the self-movement of these structural color-barcode micromotors could efficiently accelerate the mixing speed of the detection sample and greatly increase the probe-target interactions towards faster and more sensitive single or multiplex detection, and the magnetism of these barcode micromotors enables the flexible collection of the micromotors, which could facilitate the detection processes. These features make the stomatocyte structural color-barcode micromotors ideal for biomedical applications.