Development and challenges of smart actuators based on water-responsive materials.

Water-responsive (WR) materials, due to their controllable mechanical response to humidity without energy actuation, have attracted lots of attention to the development of smart actuators. WR material-based smart actuators can transform natural humidity to a required mechanical motion and have been widely used in various fields, such as soft robots, micro-generators, smart building materials, and textiles. In this paper, the development of smart actuators based on different WR materials has been reviewed systematically. First, the properties of different biological WR materials and the corresponding actuators are summarized, including plant materials, animal materials, and microorganism materials. Additionally, various synthetic WR materials and their related applications in smart actuators have also been introduced in detail, including hydrophilic polymers, graphene oxide, carbon nanotubes, and other synthetic materials. Finally, the challenges of the WR actuator are analyzed from the three perspectives of actuator design, control methods, and compatibility, and the potential solutions are also discussed. This paper may be useful for the development of not only soft actuators that are based on WR materials, but also smart materials applied to renewable energy.

Characterization of microbiota in acute leukemia patients following successful remission induction chemotherapy without antimicrobial prophylaxis.

PURPOSE: In the present study, we characterized the microbiomes of acute leukemia (AL) patients who achieved complete remission following remission induction chemotherapy (RIC) as outpatients, but who did not receive antimicrobials to treat or prevent febrile neutropenia. METHODS: Saliva and stool samples from 9 patients with acute myeloid leukemia, 11 patients with acute lymphoblastic leukemia, and 5 healthy controls were subjected to 16S ribosomal RNA sequencing at baseline and at 3 months following RIC. Only patients who achieved remission at 3 months post-treatment were included. We excluded anyone who used antimicrobials within 2 months of enrollment or at any time during the study period. RESULTS: At baseline, the relative abundances of species of Prevotella maculosa (P=0.001), Megasphaera micronuciformis (P=0.014), Roseburia inulinivorans (P=0.021), and Bacteroides uniformis (P=0.004) in saliva and Prevotella copri (P=0.002) in the stools of controls were significantly higher than in AL patients. Following RIC, the relative abundances of Eubacterium sp. oral clone DO008 (P=0.012), Leptotrichia sp. oral clone IK040 (P=0.002), Oribacterium sp. oral taxon 108 (P=0.029), Megasphaera micronuciformis (P=0.016), TM7 phylum sp. oral clone DR034 (P<0.001), Roseburia inulinivorans (P=0.034), Actinomyces odontolyticus (P=0.014), Leptotrichia buccalis (P=0.005), and Prevotella melaninogenica (P=0.046) in saliva and Lactobacillus fermentum (P=0.046), Coprococcus catus (P=0.050), butyrate-producing bacterium SS3/4 (P=0.013), and Bacteroides coprocola (P=0.027) in the stools of AL patients were significantly greater than in controls. CONCLUSION: Following RIC, several taxa are changed in stool and salvia samples of AL patients. Our results warrant future large-scale multicenter studies to examine whether the microbiota might have an effect on clinical outcomes of AL patients.

Facile modulation of cell adhesion to a poly(ethylene glycol) diacrylate film with incorporation of polystyrene nano-spheres.

Poly(ethylene glycol) diacrylate (PEGDA) is a common hydrogel that has been actively investigated for various tissue engineering applications owing to its biocompatibility and excellent mechanical properties. However, the native PEGDA films are known for their bio-inertness which can hinder cell adhesion, thereby limiting their applications in tissue engineering and biomedicine. Recently, nano composite technology has become a particularly hot topic, and has led to the development of new methods for delivering desired properties to nanomaterials. In this study, we added polystyrene nano-spheres (PS) into a PEGDA solution to synthesize a nano-composite film and evaluated its characteristics. The experimental results showed that addition of the nanospheres to the PEGDA film not only resulted in modification of the mechanical properties and surface morphology but further improved the adhesion of cells on the film. The tensile modulus showed clear dependence on the addition of PS, which enhanced the mechanical properties of the PEGDA-PS film. We attribute the high stiffness of the hybrid hydrogel to the formation of additional cross-links between polymeric chains and the nano-sphere surface in the network. The effect of PS on cell adhesion and proliferation was evaluated in L929 mouse fibroblast cells that were seeded on the surface of various PEGDA-PS films. Cells density increased with a larger PS concentration, and the cells displayed a spreading morphology on the hybrid films, which promoted cell proliferation. Impressively, cellular stiffness could also be modulated simply by tuning the concentration of nano-spheres. Our results indicate that the addition of PS can effectively tailor the physical and biological properties of PEGDA as well as the mechanical properties of cells, with benefits for biomedical and biotechnological applications.

Selective pattern of cancer cell accumulation and growth using UV modulating printing of hydrogels.

Fabrication of extracellular microenvironment for cancer cell growth in vitro is an indispensable technique to precisely control the cell spatial arrangement and proliferation for cell-behavior research. Current micropatterning methods usually require relatively complicated operations, which makes it difficult to investigate the effects of different cell growth patterns. This manuscript proposes a DMD-based projection technique to quickly pattern a poly(ethylene) glycol diacrylate (PEGDA)-based hydrogel on a common glass substrate. Using this method, we can effectively control the growth patterns of cells. Compared with these traditional methods which employ digital dynamic mask, polymerization of PEGDA solution can be used to create arbitrary shaped microstructures with high efficiency, flexibility and repeatability. The duration of UV exposure is less than 10 s through controlling the projected illumination pattern. The ability of patterned PEGDA-coated film to hinder cell adhesion makes it possible to control area over which cells attach. In our experiments, we take advantage of the blank area to pattern cells, which allows cells to grow in various pre-designed shapes and sizes. And the patterning cells have a high viability after culturing for several days. Interestingly, we found that the restricted space could stiffen and strengthen the cells. These results indicate that cells and extracellular microenvironment can influence each other.

Density Regulation and Localization of Cell Clusters by Self-Assembled Femtosecond-Laser-Fabricated Micropillar Arrays.

Tumor cell clusters of varying sizes and densities have different metastatic potentials. Three-dimensional (3D) patterned structures with rational topographical and mechanical properties are capable of guiding the 3D clustering of tumor cells. In this study, single femtosecond laser pulses were used to fabricate individual high-aspect-ratio micropillars via two-photon polymerization (TPP). By combining this approach with capillary-force self-assembly, complex 3D microstructure patterns were constructed with a high efficiency. The microstructures were able to regulate the formation of cell clusters at different cell seeding densities and direct self-guided 3D assembly of cell clusters of various sizes and densities. Localization of cell clusters was achieved using grid-indexed samples to address individual cell clusters, which holds great promise for in situ cell cluster culture and monitoring and for applications such as RNA sequencing of cell clusters.

Composite Nanostructures and Adhesion Analysis of Natural Plant Hydrogels Investigated by Atomic Force Microscopy.

Hydrogels designed by biomimetism and bioinspiration have been considered as a promising biomaterial for biomedical applications due to their biocompatible characteristics. Though biomimetic or bioinspired hydrogels have been widely studied by biochemical analysis, so far the detailed organizations and properties of native natural hydrogels are still not fully understood. The advent of atomic force microscopy (AFM) provides a potent tool for probing the biological samples in their living states with nanometer spatial resolution, which offers new possibilities for addressing the biological and material issues at the nanoscale. In this paper, AFM was utilized to characterize the structures and adhesive properties of the natural hydrogels produced by the carnivorous plant sundew. AFM morphological images of the mucilage secreted by three types of sundew show the composite nanostructures of the mucilage (e.g., nanoparticles, nanofibers, and porous polymeric networks), which are correlated with the mucilage's adhesive features revealed by AFM force measurements and peak force tapping mechanical imaging. The research demonstrates the prominent capabilities of AFM in characterizing the nanoscopic structures and properties of natural hydrogels with unprecedented spatial resolution, which is useful for understanding the underlying mechanisms guiding the behaviors of natural hydrogels and will potentially benefit the studies of biomimetic and bioinspired biomaterials.

Hydrogel Printing Based on UV-Induced Projection for Cell-Based Microarray Fabrication.

A considerable number of studies have focused on fabrication of hydrogel microstructures due to its wide applications in tissue engineering, drug delivery, and extracellular matrix construction. Here, we introduce a hydrogel printing method based on UV-induced projection via a digital micromirror device (DMD). Arbitrary microstructures could be fabricated within few seconds (<3) by modulating UV projection using DMD as digital dynamic masks instead of a physical mask, which also offers a high degree of flexibility and repeatability. Furthermore, the ability of PEGDA film to hinder cell adhesion makes it possible to control area over which cells attach.

Visible light induced electropolymerization of suspended hydrogel bioscaffolds in a microfluidic chip.

The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.

Regulation of breast cancer cell behaviours by the physical microenvironment constructed via projection microstereolithography.

A considerable number of studies have examined how intrinsic factors regulate breast cancer cell behaviours; however, physical microenvironmental cues may also modulate cellular morphology, proliferation, and migration and mechanical properties. In the present study, the surrounding microenvironment of breast cancer cells was constructed using projection microstereolithography, enabling the investigation of the external environment's effects on breast cancer cell behaviours. A poly(ethylene) glycol diacrylate (PEGDA) solution was polymerized by programmable ultraviolet exposure to create arbitrary shapes with high biocompatibility, efficiency, flexibility and repeatability, and the resistance to cell attachment enabled the PEGDA coated film to hinder cell adhesion, allowing cells to grow in specific patterns. Furthermore, breast cancer cell morphology and mechanical properties were modified by altering the microenvironment. Proliferation was higher in breast cancer as compared to normal cells, consistent with the primary characteristic of malignant tumors. Moreover, breast cancer cells migrated more rapidly when grown in a narrow channel as compared to a wider channel. These findings enhance our understanding of the role of the microenvironment in breast cancer cell behaviours and can provide a basis for developing effective anticancer therapies.

Amplitude Modulation Mode of Scanning Ion Conductance Microscopy.

Live-cell imaging at the nanoscale resolution is a hot research topic in the field of life sciences for the direct observation of cellular biological activity. Scanning ion conductance microscopy (SICM) is one of the few effective imaging tools for live-cell imaging at the nanoscale resolution. However, there are various problems in existing scanning modes. The hopping and AC modes suffer from low speed, whereas the DC mode is prone to instability because of the DC drift and external electrical interference. In this article, we propose an amplitude modulation (AM) mode of SICM, which employs an AC voltage to enhance the stability and improve the scanning speed. In this AM mode, we introduce a capacitance compensation method to eliminate capacitance effect and use the amplitude of the AC current component to control the tip movement. Experimental results on polydimethylsiloxane samples verify the validity of the AM mode and demonstrate an improved performance of both speed and stability of this new mode.

Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics.

The culturing of cancer cells on micropatterned substrates can provide insight into the factors of the extracellular environment that enable the control of cell growth. We report here a novel non-UV-based technique to quickly micropattern a poly-(ethylene) glycol diacrylate (PEGDA)-based hydrogel on top of modified glass substrates, which were then used to control the growth patterns of breast cancer cells. Previously, the fabrication of micropatterned substrates required relatively complicated steps, which made it impractical for researchers to rapidly and systematically investigate the effects of different cell growth patterns. The technique presented herein operates on the principle of optically-induced electrokinetics (OEKs) and uses computer-generated projection light patterns to dynamically pattern the hydrogel on a hydrogenated amorphous silicon (a-Si:H) thin-film, atop an indium tin oxide (ITO) glass substrate. This technique allows us to pattern lines, circles, pentagons, and more complex shapes in the hydrogel with line widths below 3 µm and thicknesses of up to 6 µm within 8 s by simply controlling the projected illumination pattern and applying an appropriate AC voltage between the two ITO glass substrates. After separating the glass substrates to expose the patterned hydrogel, we experimentally demonstrate that MCF-7 breast cancer cells will adhere to the bare a-Si:H surface, but not to the hydrogel patterned in various geometric shapes and sizes. Theoretical analysis and finite-element model simulations reveal that the dominant OEK forces in our technique are the dielectrophoresis (DEP) force and the electro-osmosis force, which enhance the photo-initiated cross-linking reaction in the hydrogel. Our preliminary cultures of breast cancer cells demonstrate that this reported technique could be applied to effectively confine the growth of cancer cells on a-Si:H surfaces and affect individual cell geometry during their growth.