wileyonlinelibrary.comhydrogels exhibit slow macroscale response with a magnitude of minutes to hours. [10][11][12][13] Meanwhile, they are typically mechanically weak or brittle, [ 14,15 ] resulting in unstable performance after cycles of stimulation. In addition, most of these hydrogels possess isotropic porous structures, showing size changes evenly, making desirable locomotion (e.g., bending, twisting, and folding) diffi cult to achieve. [ 16,17 ] Modulation of pores size and their distributions is essential for manipulating hydrogels properties. Several strategies including gas foaming, [ 18 ] fi ber bonding, [ 19 ] and porogen leaching [ 20 ] were developed to fabricate homo geneous macropore sized hydrogels for rapid responses. However, the orientation responses of such materials were limited, causing diffi culties in anisotropic locomotion. Moreover, mechanical strength of these hydrogels was relatively weak due to the fragile macrosized pore structures. On the other hand, electrophoresis-assisted porogen leaching and hydrogel layering methods [21][22][23][24] have been developed to produce responsive hydrogels with stepwisedistributed pore structures to enable their anisotropic responsive capabilities. However, these hydrogels have some adverse properties including less pore interconnectivity, decelerated mass transport, and being prone to delamination, causing their slow response to stimuli and poor mechanical properties. To date, synthesis of hydrogels with simultaneously rapid thermal response kinetics, robust mechanical strength, and desirable anisotropic locomotion remains an unsolved challenge.In this study, we presented a heterobifunctional crosslinker enabled hydrothermal process, forming hydrogels with gradient porous structure to address these issues. The hydrothermal synthesis is performed in closed systems of relatively high temperatures and pressures, in which only water is used as the reactive medium. At elevated temperatures, hydrothermal process can prompt a variety of chemical reactions such as vinyl polymerizations and intermolecular dehydration. [25][26][27] N -isopropylacrylamide (NIPAM), a well-known thermo-responsive material bearing two highly reactive double bonds, [ 28,29 ] was used as monomer. 4-hydroxybutyl acrylate (4HBA), an acrylic ester possessing a reactive double bond and a less reactive hydroxyl group at either end of the molecule, was innovatively applied Programmable locomotion of responsive hydrogels has gained increasing attention for potential applications in soft robotics, microfl uidic components, actuators, and artifi cial muscle. Modulation of hydrogel pore structures is essential for tailoring their mechanical strength, response speeds, and motion behaviors. Conventional methods forming hydrogels with homogeneous or stepwise-distributed pore structures are limited by the required compromise to simultaneously optimize these aspects. Here, a heterobifunctional crosslinker enabled hydrothermal process is introduced to synthesize responsive hydrogels with well-defi...

In this paper we present compartmentalized neuron arraying (CNA) microfluidic circuits for the preparation of neuronal networks using minimal cellular inputs (10-100-fold less than existing systems).The approach combines the benefits of microfluidics for precision single cell handling with biomaterial patterning for the long term maintenance of neuronal arrangements. A differential flow principle was used for cell metering and loading along linear arrays. An innovative water masking technique was developed for the inclusion of aligned biomaterial patterns within the microfluidic environment. For patterning primary neurons the technique involved the use of meniscus-pinning micropillars to align a water mask for plasma stencilling a poly-amine coating. The approach was extended for patterning the human SH-SY5Y neuroblastoma cell line using a poly(ethylene glycol) (PEG) back-fill and for dopaminergic LUHMES neuronal precursors by the further addition of a fibronectin coating. The patterning efficiency E patt was .75% during lengthy in chip culture, with y85% of the outgrowth channels occupied by neurites. Neurons were also cultured in next generation circuits which enable neurite guidance into all outgrowth channels for the formation of extensive inter-compartment networks. Fluidic isolation protocols were developed for the rapid and sustained treatment of the different cellular and sub-cellular compartments. In summary, this research demonstrates widely applicable microfluidic methods for the construction of compartmentalized brain models with single cell precision. These minimalistic ex vivo tissue constructs pave the way for high throughput experimentation to gain deeper insights into pathological processes such as Alzheimer and Parkinson Diseases, as well as neuronal development and function in health.

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.

Achieving efficient photon upconversion under low irradiance is not only a fundamental challenge but also central to numerous advanced applications spanning from photovoltaics to biophotonics. However, to date, almost all approaches for upconversion luminescence intensification require stringent controls over numerous factors such as composition and size of nanophosphors. Here, we report the utilization of dielectric microbeads to significantly enhance the photon upconversion processes in lanthanide-doped nanocrystals. By modulating the wavefront of both excitation and emission fields through dielectric superlensing effects, luminescence amplification up to 5 orders of magnitude can be achieved. This design delineates a general strategy to converge a low-power incident light beam into a photonic hotspot of high field intensity, while simultaneously enabling collimation of highly divergent emission for far-field accumulation. The dielectric superlensing-mediated strategy may provide a major step forward in facilitating photon upconversion processes toward practical applications in the fields of photobiology, energy conversion, and optogenetics.

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.