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.

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.

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.

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.

Photoresponsive microvalve for remote actuation and flow control in microfluidic devices.

Microvalves with different actuation methods offer great integrability and flexibility in operation of lab-on-chip devices. In this work, we demonstrate a hydrogel-based and optically controlled modular microvalve that can be easily integrated within a microfluidic device and actuated by an off-chip laser source. The microvalve is based on in-channel trapping of microgel particles, which are composed of poly(N-isopropylacrylamide) and polypyrrole nanoparticles.

Remote modulation of neural activities via near-infrared triggered release of biomolecules.

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules.

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.

A one-step hydrothermal route to programmable stimuli-responsive hydrogels.

A hydrothermal route to regulate the swelling and responsiveness properties of poly(N-isopropylacrylamide) (PNIPAM) hydrogels is reported. During the process, water is the only reactive medium used, and the hydrogel properties can be programmed effectively.

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.

Near-infrared light triggerable deformation-free polysaccharide double network hydrogels.

To prepare a hydrogel with robust mechanical properties and programmable remotely-controlled releasing ability, we synthesized an agarose/alginate double network hydrogel incorporating polypyrrole (PPy) nanoparticles as a near-infrared (NIR) laser responsive releasing system. This hydrogel exhibited pulsatile releasing behaviours according to the laser switching while maintaining its morphology and mechanical strength.

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 neuron's 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.

Near-infrared photothermal activation of microgels incorporating polypyrrole nanotransducers through droplet microfluidics.

Poly(N-isopropylacrylamide) (pNIPAM) composite microgels incorporating polypyrrole (PPy) nanoparticles were produced using droplet microfluidics. The composite microgels exhibited site-specific de-swelling-swelling properties that were activated by near-infrared light. Their applications for programmable drug release by pulsed-light control were also demonstrated.

Layer-by-layer polyelectrolyte-polyester hybrid microcapsules for encapsulation and delivery of hydrophobic drugs.

A two-step process is developed to form layer-by-layer (LbL) polyelectrolyte microcapsules, which are able to encapsulate and deliver hydrophobic drugs. Spherical porous calcium carbonate (CaCO3) microparticles were used as templates and coated with a poly(lactic acid-co-glycolic acid) (PLGA) layer containing hydrophobic compounds via an in situ precipitation gelling process. PLGA layers that precipitated from N-methyl-2-pyrrolidone (NMP) had a lower loading and smoother surface than those precipitated from acetone.

Surface functionalization of nanoparticles to control cell interactions and drug release.

Nanoparticles made from poly(dl-lactide-co-glycolide) (PLGA) are used to deliver a wide range of bioactive molecules, due to their biocompatibility and biodegradability. This study investigates the surface modification of PLGA nanoparticles via the layer-by-layer (LbL) deposition of polyelectrolytes, and the effects of these coatings on the release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency. PLGA nanoparticles are modified via LbL adsorption of two polyelectrolyte pairs: 1) poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) and 2) poly(L-lysine hydrobromide) (PLL) and dextran sulfate (DES).

Engineering of erythrocyte-based drug carriers: control of protein release and bioactivity.

This work reports the fabrication of layer-by-layer (LbL) polyelectrolyte coated erythrocyte carriers that provide a simple means for controlling the burst and subsequent release of lysozyme. Erythrocytes were loaded with RITC-lysozyme as model compound via the hypotonic dialysis method. An encapsulation efficiency of 41.

Layer-by-layer microcapsules templated on erythrocyte ghost carriers.

This work reports the fabrication of layer-by-layer (LbL) microcapsules that provide a simple mean for controlling the burst and subsequent release of bioactive agents. Red blood cell (RBC) ghosts were loaded with fluorescently labeled dextran and lysozyme as model compounds via hypotonic dialysis with an encapsulation efficiency of 27-31%. It is demonstrated that these vesicles maintain their shape and integrity and that a uniform distribution of the encapsulated agents within these carriers is achieved.

Effects of oligo(3-hydroxyalkanoates) on the viability and insulin secretion of murine beta cells.

Biopolyesters of polyhydroxyalkanoates (PHAs), including poly-3-hydroxybutyrate (PHB), co-polyester of 3-hydroxybutyrate and 4-hydroxybutyrate (P3HB4HB), and co-polyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) have been well investigated for their biocompatibility. For in vivo application, it is very important that the degradation products of PHAs, especially the oligomers, are not harmful to the cells and surrounding tissues. In this study, in vitro effects of oligo(3-hydroxybutyrate) (OHB), oligo(3-hydroxybutyrate-co-4-hydroxybutyrate) (O3HB4HB) and oligo(3-hydroxybutyrate-co-3-hydroxyhexanoate) (OHBHHx) on growth and differentiation of the murine beta cell line NIT-1 were investigated.

Application of (R)-3-hydroxyalkanoate methyl esters derived from microbial polyhydroxyalkanoates as novel biofuels.

Microbial polyhydroxyalkanoates (PHA) were proposed for the first time as a new type of biofuel. In this paper, poly-R-3-hydroxybutyrate (PHB) and medium chain length PHA (mcl PHA) were, respectively, esterified to become R-3-hydroxybutyrate methyl ester (3HBME) and medium chain length hydroxyalkanoate methyl ester (3HAME) via acid-catalyzed hydrolysis. The recovery percentages of 3HBME and 3HAME were 52 and 65%, respectively.