Rongcong Luo

Near‐Infrared Light Responsive Multi‐Compartmental Hydrogel Particles Synthesized Through Droplets Assembly Induced by Superhydrophobic Surface

Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed.

NeuroArray: A Universal Interface for Patterning and Interrogating Neural Circuitry with Single Cell Resolution

Recreation of neural network in vitro with designed topology is a valuable tool to decipher how neurons behave when interacting in hierarchical networks. In this study, we developed a simple and effective platform to pattern primary neurons in array formats for interrogation of neural circuitry with single cell resolution. Unlike many surface-chemistry-based patterning methods, our NeuroArray technique is specially designed to accommodate neurons polarized morphologies to make regular arrays of cells without restricting their neurite outgrowth, and thus allows formation of freely designed, well-connected, and spontaneously active neural network. The NeuroArray device was based on a stencil design fabricated using a novel sacrificial-layer-protected PDMS molding method that enables production of through-structures in a thin layer of PDMS with feature sizes as small as 3 µm. Using the NeuroArray along with calcium imaging, we have successfully demonstrated large-scale tracking and recording of neuronal activities, and used such data to characterize the spiking dynamics and transmission within a diode-like neural network. Essentially, the NeuroArray is a universal patterning platform designed for, but not limited to neuron cells. With little adaption, it can be readily interfaced with other interrogation modalities for high-throughput drug testing, and for building neuron culture based live computational devices.

Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules.

Production of Hollow Bacterial Cellulose Microspheres Using Microfluidics to Form an Injectable Porous Scaffold for Wound Healing

Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core-shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long-term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal-chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound-healing in a Sprague Dawley rat skin model.

Heterogeneous multi-compartmental hydrogel particles as synthetic cells for incompatible tandem reactions

In nature, individual cells contain multiple isolated compartments in which cascade enzymatic reactions occur to form essential biological products with high efficiency. Here, we report a cell-inspired design of functional hydrogel particles with multiple compartments, in which different enzymes are spatially immobilized in distinct domains that enable engineered, one-pot, tandem reactions. The dense packing of different compartments in the hydrogel particle enables effective transportation of reactants to ensure that the products are generated with high efficiency. To demonstrate the advantages of micro-environmental modifications, we employ the copolymerization of acrylic acid, which leads to the formation of heterogeneous multi-compartmental hydrogel particles with different pH microenvironments. Upon the positional assembly of glucose oxidase and magnetic nanoparticles, these hydrogel particles are able to process a glucose-triggered, incompatible, multistep tandem reaction in one pot. Furthermore, based on the high cytotoxicity of hydroxyl radicals, a glucose-powered therapeutic strategy to kill cancer cells was approached.Cells contain isolated compartments where cascade enzymatic biochemical reactions occur to form essential biological products with high efficiency. Here the authors produce functional hydrogel particles with multiple compartments via microfluidics that contain spatially immobilized natural enzymes in distinct domains for one-pot, tandem reactions.

Effective Light Directed Assembly of Building Blocks with Microscale Control

Light-directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high-throughput light-directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light-guided locations, forming desired patterns. With the advantage of effective light-directed assembly, the microfluidic-fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem-cell-seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold-free tissues with desired structures. This light-directed fabrication method can be applied to integrate different building units, enabling the bottom-up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.

Fast-responsive hydrogel as an injectable pump for rapid on-demand fluidic flow control

Chemically synthesized functional hydrogels have been recognized as optimized soft pumps for on-demand fluidic regulation in micro-systems. However, the challenges regarding the slow responses of hydrogels have very much limited their application in effective fluidic flow control. In this study, a heterobifunctional crosslinker (4-hydroxybutyl acrylate)-enabled two-step hydrothermal phase separation process for preparing a highly porous hydrogel with fast response dynamics was investigated for the fabrication of novel microfluidic functional units, such as injectable valves and pumps. The cylinder-shaped hydrogel, with a diameter of 9 cm and a height of 2.5 cm at 25 °C, achieved a size reduction of approximately 70% in less than 30 s after the hydrogels were heated at 40 °C. By incorporating polypyrrole nanoparticles as photothermal transducers, a photo-responsive composite hydrogel was approached and exhibited a remotely triggerable fluidic regulation and pumping ability to generate significant flows, showing on-demand water-in-oil droplet generation by laser switching, whereby the droplet size could be tuned by adjusting the laser intensity and irradiation period with programmable manipulation.