Histidine-Triggered GO Hybrid Hydrogels for Microfluidic 3D Printing

Graphene oxide (GO) hydrogels have provided tremendous opportunities in designing and fabricating complex constructs for diverse applications, while their 3D printing without photocuring is still a challenging task due to their low viscosity, uncontrollable gelation, and low interfacial tension. Here, we report a histidine-assisted printing strategy to prepare GO hybrid hydrogels through the microfluidic 3D printing technique. We found that the GO additive could significantly hamper the Knoevenagel condensation (KC) reaction between benzaldehyde and cyanoacetate group-functionalized polymers to form a hydrogel, while these GO mixed solutions were rapidly solidified into a hydrogel when histidine was added. This fascinating phenomenon enabled us to prepare low-viscosity GO mixed polymer solutions as printable inks and generate hydrogel microfibers in histidine solutions. The hydrogel fibers could support cell survival and be further constructed into complex 3D structures through microfluidic 3D printing techniques. Moreover, due to the addition of GO, the microfibers exhibited excellent electrical conductivity and could sense the motion changes and convert these stimuli as electrical resistance signals. This strategy adds an option for the design and application of 3D printable aqueous GO inks in many fields

Noninvasive Multiplexed Analysis of Bladder Cancer-Derived Urine Exosomes via Janus Magnetic Microspheres

Bladder cancer greatly endangers human health, and its early diagnosis is of vital importance. Exosomes, which contain proteins and nucleic acids related to their source cells, are expected to be an emerging biomarker for bladder cancer detection. Here, we propose a novel system for multiplexed analysis of bladder cancer-derived urine exosomes based on Janus magnetic microspheres as barcoded microcarriers. The microcarriers are constructed by droplet-templated coassembly of colloidal silica nanoparticles and magnetic nanoparticles under a magnetic field. The microcarriers possess one hemisphere with structural color and the other hemisphere with magneto-responsiveness. Benefiting from the unique structure, these Janus microcarriers could serve as barcodes and could move controllably in a sample solution, thus realizing the multiplex detection of exosomes with high sensitivity. Notably, the present platform is noninvasive since a urine specimen, as an ideal source of bladder cancer-derived exosomes, is employed as the sample solution. This feature, together with the good sensitivity, specificity, low sample consumption, and easy operation, indicates the great potential of the platform for bladder cancer diagnosis in clinical applications

Photonic Crystal Microbubbles as Suspension Barcodes

A novel suspension array was developed that uses photonic crystal (PhC) microbubbles as barcode particles. The PhC microbubbles have an outer transparent polymeric shell, a middle PhC shell, and an inner bubble core, and they were achieved by extraction-derived self-assembly of colloidal nanoparticles in semipermeable solid microcapsules. The encoded elements of the microbubbles originated from their PhC structure with a coated shell, which not only improved the stability of the codes but also provided a flexible surface for bioassays. By using multicompartmental microcapsule templates, PhC microbubbles with substantial coding levels and controllable movement could also be achieved. In addition, as the size of the encapsulated bubbles could be tailored, the overall density of the PhC microbubbles could be adjusted to match the density of a detection solution and to remain in suspension. These remarkable properties make the PhC microbubbles excellent barcode particles

Structural Color Patterns by Electrohydrodynamic Jet Printed Photonic Crystals

In this work, we demonstrate the fabrication of photonic crystal patterns with controllable morphologies and structural colors utilizing electrohydrodynamic jet (E-jet) printing with colloidal crystal inks. The final shape of photonic crystal units is controlled by the applied voltage signal and wettability of the substrate. Optical properties of the structural color patterns are tuned by the self-assembly of the silica nanoparticle building blocks. Using this direct printing technique, it is feasible to print customized functional patterns composed of photonic crystal dots or photonic crystal lines according to relevant printing mode and predesigned tracks. This is the first report for E-jet printing with colloidal crystal inks. Our results exhibit promising applications in displays, biosensors, and other functional devices

Controlled Fabrication of Bioactive Microfibers for Creating Tissue Constructs Using Microfluidic Techniques

The fabrication of heterogeneous microstructures, which exert precise control over the distribution of different cell types within biocompatible constructs, is important for many tissue engineering applications. Here, bioactive microfibers with tunable morphologies, structures, and components are generated and employed for creating different tissue constructs. Multibarrel capillary microfluidics with multiple laminar flows are used for continuously spinning these microfibers. With an immediate gelation reaction of the cell dispersed alginate solutions, the cell-laden alginate microfibers with the tunable morphologies and structures as the designed multiple laminar flows can be generated. The performances of the microfibers in cell culture are improved by incorporating bioactive polymers, such as extracellular matrix (ECM) or methacrylated gelatin (GelMA), into the alginate. It is demonstrated that a series of complex three-dimensional (3D) architectural cellular buildings, including biomimic vessels and scaffolds, can be created using these bioactive microfibers

Photonic Crystal Microbubbles as Suspension Barcodes

A novel suspension array was developed that uses photonic crystal (PhC) microbubbles as barcode particles. The PhC microbubbles have an outer transparent polymeric shell, a middle PhC shell, and an inner bubble core, and they were achieved by extraction-derived self-assembly of colloidal nanoparticles in semipermeable solid microcapsules. The encoded elements of the microbubbles originated from their PhC structure with a coated shell, which not only improved the stability of the codes but also provided a flexible surface for bioassays. By using multicompartmental microcapsule templates, PhC microbubbles with substantial coding levels and controllable movement could also be achieved. In addition, as the size of the encapsulated bubbles could be tailored, the overall density of the PhC microbubbles could be adjusted to match the density of a detection solution and to remain in suspension. These remarkable properties make the PhC microbubbles excellent barcode particles

Cells Cultured on Core–Shell Photonic Crystal Barcodes for Drug Screening

The development of effective drug screening platforms is an important task for biomedical engineering. Here, a novel methacrylated gelatin (GelMA) hydrogel-encapsulated core–shell photonic crystal (PhC) barcode particle was developed for three-dimensional cell aggregation culture and drug screening. The GelMA shells of the barcode particles enable creation of a three-dimensional extracellular matrix (ECM) microenvironment for cell adhesion and growth, while the PhC cores of the barcode particles provide stable diffraction peaks that can encode different cell spheroids during culture and distinguish their biological response during drug testing. The applicability of this cell spheroids-on-barcodes platform was investigated by testing the cytotoxic effect of tegafur (TF), a prodrug of 5-fluorouracil (5-FU), on barcode particle-loaded liver HepG2 and HCT-116 colonic tumor cell spheroids. The cytotoxicity of TF against the HCT-116 tumor cell spheroids was enhanced in systems using cocultures of HepG2 and NIH-3T3 cells, indicating the effectiveness of this multiple cell spheroids-on-barcodes platform for drug screening

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs