nru Yu

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.

Bioinspired Helical Microfibers from Microfluidics

Helical objects are among the most important and landmark structures in nature, and represent an emerging group of materials with unique spiral geometry; because of their enriched physical and chemical properties, they can have multiple functionalities. However, the fabrication of such complex helical materials at the micro- or nanoscale level remains a challenge. Here, a coaxial capillary microfluidic system, with the functions of consecutive spinning and spiraling, is presented for scalable generation of helical microfibers. The generation processes can be precisely tuned by adjusting the flow rates, and thus the length, diameter, and pitch of the helical microfibers are highly controllable. Varying the injection capillary design of the microfluidics enables the generation of helical microfibers with structures such as the novel Janus, triplex, core-shell, and even double-helix structures. The potential use of these helical microfibers is also explored for magnetically and thermodynamically triggered microsprings, as well as for a force indicator for contraction of cardiomyocytes. These indicate that such helical microfibers are highly versatile for different applications.

Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics.

Heterostructured microfibers with spindle-knots and joints are developed using a novel microfluidic technology, which enables integrative microfiber joint spinning, fluid coating, and knot emulsification. The knots emulsification process can be precisely tunable by adjusting the flow rates. In this way, the size and spacing of the spindle-knots of the microfibers can be achieved with high controllability. More attractively, the construction process benefits from the broad availability of the coating fluids, which determines the compositions of the knots. Thus, the resultant microfibers are imparted with distinctive functions, such as humidity-responsive water capture, thermally triggered water convergence, induced colloidal crystal assembly, and cell microcarrier arrays. These features make such microfibers highly versatile for use in diverse applications.

Microfluidic Generation of Porous Microcarriers for Three-Dimensional Cell Culture

Inspired by the microstructure of the stem cell niche, which is generally composed of adjacent cell protection layers and an extracellular matrix (ECM), we present novel microfluidic porous microcarriers for cell culture that consist of external-internal connected scaffold structures and biopolymer matrix fillers. The biomimetic scaffold structure of the porous microcarriers not only avoids the imposition of shear forces on the encapsulated cells but also provides a confined microenvironment for cell self-assembly, whereas the biopolymers in the porous cores of the microcarriers can act as an ECM microenvironment to promote the formation of multicellular spheroid aggregates for biomedical applications.

Bioinspired living structural color hydrogels

Robotic objects and “heart-on-a-chip” platforms feature bioinspired structural color materials with autonomous regulation. Structural color materials from existing natural organisms have been widely studied to enable artificial manufacture. Variable iridescence has attracted particular interest because of the displays of various brilliant examples. Existing synthetic, variable, structural color materials require external stimuli to provide changing displays, despite autonomous regulation being widespread among natural organisms, and therefore suffer from inherent limitations. Inspired by the structural color regulation mechanism of chameleons, we present a conceptually different structural color material that has autonomic regulation capability by assembling engineered cardiomyocyte tissues on synthetic inverse opal hydrogel films. The cell elongation and contraction in the beating processes of the cardiomyocytes caused the inverse opal structure of the substrate film to follow the same cycle of volume or morphology changes. This was observed as the synchronous shifting of its photonic band gap and structural colors. Such biohybrid structural color hydrogels can be used to construct a variety of living materials, such as two-dimensional self-regulating structural color patterns and three-dimensional dynamic Morpho butterflies. These examples indicated that the stratagem could provide an intrinsic color-sensing feedback to modify the system behavior/action for future biohybrid robots. In addition, by integrating the biohybrid structural color hydrogels into microfluidics, we developed a “heart-on-a-chip” platform featuring microphysiological visuality for biological research and drug screening. This biohybrid, living, structural color hydrogel may be widely used in the design of a variety of intelligent actuators and soft robotic devices.

Bioinspired Heterogeneous Structural Color Stripes from Capillaries

As an important characteristic of many creatures, structural colors play a crucial role in the survival of organisms. Inspired by these features, an intelligent structural color material with a heterogeneous striped pattern and stimuli-responsivity by fast self-assembly of colloidal nanoparticles in capillaries with a certain diameter range are presented here. The width, spacing, color, and even combination of the structural color stripe patterns can be precisely tailored by adjusting the self-assembly parameters. Attractively, with the integration of a near-infrared (NIR) light responsive graphene hydrogel into the structural color stripe pattern, the materials are endowed with light-controlled reversible bending behavior with self-reporting color indication. It is demonstrated that the striped structural color materials can be used as NIR-light-triggered dynamic barcode labels for the anti-counterfeiting of different products. These features of the bioinspired structural color stripe pattern materials indicate their potential values for mimicking structural color organisms, which will find important applications in constructing intelligent sensors, anti-counterfeiting devices, and so on.

Microfluidic Lithography of Bioinspired Helical Micromotors

Considerable efforts have been devoted to developing artificial micro/nanomotors that can convert energy into movement. A flow lithography integrated microfluidic spinning and spiraling system is developed for the continuous generation of bioinspired helical micromotors. Because the generation processes could be precisely tuned by adjusting the flow rates and the illuminating frequency, the length, diameter, and pitch of the helical micromotors were highly controllable. Benefiting from the fast online gelation and polymerization, the resultant helical micromotors could be imparted with Janus, triplex, and core-shell cross-sectional structures that have never been achieved by other methods. Owing to the spatially controlled encapsulation of functional nanoparticles in the microstructures, the helical micromotors can perform locomotion not only by magnetically actuated rotation or corkscrew motion but also through chemically powered catalytic reaction.

Bio-inspired stimuli-responsive graphene oxide fibers from microfluidics

Graphene oxide (GO) fibers with a spindle-knotted structure and photothermally responsive phase-transition behaviors were fabricated by combining spinning and emulsification procedures in microfluidics. The resultant GO fibers enabled fog-capture and NIR-triggered water-collection applications.

Egg Component-Composited Inverse Opal Particles for Synergistic Drug Delivery

Microparticles have a demonstrated value in drug delivery systems. The attempts to develop this technology focus on the generation of functional microparticles by using innovative but accessible materials. Here, we present egg component-composited microparticles with a hybrid inverse opal structure for synergistic drug delivery. The egg component inverse opal particles were produced by using egg yolk to negatively replicate colloid crystal bead templates. Because of their huge specific surface areas, abundant nanopores, and complex nanochannels of the inverse opal structure, the resultant egg yolk particles could be loaded with different kinds of drugs, such as hydrophobic camptothecin (CPT), by simply immersing them into the corresponding drug solutions. Attractively, additional drugs, such as the hydrophilic doxorubicin (DOX), could also be encapsulated into the particles through the secondary filling of the drug-doped egg white hydrogel into the egg yolk inverse opal scaffolds, which realized the synergistic drug delivery for the particles. It was demonstrated that the egg-derived inverse opal particles were with large quantity and lasting releasing for the CPT and DOX codelivery, and thus could significantly reduce cell viability, and enhance therapeutic efficacy in treating cancer cells. These features of the egg component-composited inverse opal microparticles indicated that they are ideal microcarriers for drug delivery.

Design of capillary microfluidics for spinning cell-laden microfibers

This protocol describes the design of capillary microfluidics for spinning bioactive (cell-laden) microfibers for three-dimensional (3D) cell culture and tissue-engineering applications. We describe the assembly of three types of microfluidic systems: (i) simple injection capillary microfluidics for the spinning of uniform microfibers; (ii) hierarchical injection capillary microfluidics for the spinning of core–shell or spindle-knot structured microfibers; and (iii) multi-barrel injection capillary microfluidics for the spinning of microfibers with multiple components. The diverse morphologies of these bioactive microfibers can be further assembled into higher-order structures that are similar to the hierarchical structures in tissues. Thus, by using different types of capillary microfluidic devices, diverse styles of microfibers with different bioactive encapsulation can be generated. These bioactive microfibers have potential applications in 3D cell culture, the mimicking of vascular structures, the creation of synthetic tissues, and so on. The whole protocol for device fabrication and microfiber spinning takes ~1 d.This protocol describes how to produce cell-laden microfibers using capillary microfluidic devices. The devices enable spinning of increasingly complex microfibers, which can function as building blocks for 3D cell culture and tissue engineering.