Mobile micro‐ and nanorobots are proposed for future biomedical applications, such as diagnostics and targeted delivery. For their translation to clinical practice, biocompatibility and ...biodegradability of micro‐ and nanorobots are required aspects. The fabrication of small‐scale robots with non‐cytotoxic biodegradable soft components will allow for enhanced device assimilation, optimal tissue interaction and minimized immune reactions. The 3D microfabrication of biodegradable soft helical microswimmers via two‐photon polymerization of the non‐toxic photocrosslinkable hydrogel gelatin methacryloyl (GelMA) is reported. GelMA microswimmers are fabricated with user‐defined geometry and rendered magnetically responsive by decorating their surface with magnetic nanoparticles. In contrast to previous rigid helical microrobots, the soft helical microswimmers can corkscrew above the step‐out frequency with relatively high values of forward velocity, suggesting an unprecedented self‐adaptive behavior. Cytotoxicity assays show the toxicity of GelMA is at least three orders of magnitude lower than that of poly(ethyleneglycol) diacrylates, which are widely used for fabricating hydrogel‐based microswimmers. GelMA microswimmers are fully degradable by collagenases. Furthermore, they support cell attachment and growth, and are gradually digested by cell‐released enzymes during culture. These non‐cytotoxic biodegradable hydrogel microswimmers will greatly expand their applications in medicine by eliminating the concerns of retrieving microrobots after fulfilling tasks in body.
Biodegradable soft helical microswimmers are successfully developed based on two‐photon photopolymerization of a gelatin derivative, GelMA. By decorating their surface with magnetic nanoparticles, these microswimmers can be manipulated by magnetic field. Because of the proteolytic cleavage of peptide domains in gelatin, microswimmers made of GelMA can be fully degraded by cell‐secreted proteases.
Metachronal waves commonly exist in natural cilia carpets. These emergent phenomena, which originate from phase differences between neighbouring self-beating cilia, are essential for biological ...transport processes including locomotion, liquid pumping, feeding, and cell delivery. However, studies of such complex active systems are limited, particularly from the experimental side. Here we report magnetically actuated, soft, artificial cilia carpets. By stretching and folding onto curved templates, programmable magnetization patterns can be encoded into artificial cilia carpets, which exhibit metachronal waves in dynamic magnetic fields. We have tested both the transport capabilities in a fluid environment and the locomotion capabilities on a solid surface. This robotic system provides a highly customizable experimental platform that not only assists in understanding fundamental rules of natural cilia carpets, but also paves a path to cilia-inspired soft robots for future biomedical applications.
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Reconfigurable micromachines that are highly conscious of changing environments have significant potential for use in biomedical applications, such as minimally invasive surgery, cell ...manipulation, and tissue engineering. Current nanofabrication approaches with sophisticated designs appear to enhance the controllability of shape transformations, such as bending, folding, and twisting, while minimizing the response time. However, the construction of three-dimensional (3D) structures at a small scale with a high shape-morphing freedom poses challenges because of the lack of applicable materials and effective fabrication techniques. Here, we develop an advanced four-dimensional microprinting strategy for constructing 3D-to-3D shape-morphing micromachines in a single-material-single-step mode. Using direct laser writing, heterogeneous stimulus-responsive hydrogels can be distributed spatially into arbitrary 3D shapes with sub-micrometer features. The material crosslinking densities, stiffnesses, and swelling/shrinking degrees can be modulated by programming the exposure dosage of femtosecond laser pulses and characterized to predict the shape-morphing behaviors via finite-element methods. With our proposed approach, complex 3D reconfigurable compound micromachines with mechanical advantages, which exhibit an excellent deformation-amplifying effectiveness, can be constructed to achieve a rapid, precise, and reversible 3D-to-3D shape transformation in response to multiple external stimuli, and they emerge as promising smart and multifunctional micromachine candidates for various engineering applications.
Functional compound micromachines are fabricated by a design methodology using 3D direct laser writing and selective physical vapor deposition of magnetic materials. Microtransporters with a ...wirelessly controlled Archimedes screw pumping mechanism are engineered. Spatiotemporally controlled collection, transport, and delivery of micro particles, as well as magnetic nanohelices inside microfluidic channels are demonstrated.
Gene delivery systems play a vital role in gene therapy and recombinant protein production. The advantages of using gene delivery reagents for non-viral vector include the capacity to accommodate a ...large packaging load and their low or absent immunogenicity. Furthermore, they are easy to produce at a large scale and preserve. Gene delivery reagents for non-viral vector are commonly used for transfecting a variety of cells and tissues. It is mainly composed of liposomes and non-liposome cationic polymers. According to the different head structures used, the non-viral cationic transfection reagents include a quaternary ammonium salt, amine, amino acid or polypeptide, guanidine salt, and a heterocyclic ring. This article summarizes these approaches and developments of types and components of transfection reagents and optimization of gene delivery. The optimization of mammalian cell transient recombinant protein expression system and cationic reagents for clinical or clinical trials are also discussed.
Two‐dimensional (2D) materials and ultrathin nanosheets are advantageous for elevating the catalysis performance and elucidating the catalysis mechanism of heterogeneous catalysts, but they are ...mostly restricted to inorganic or organic materials based on covalent bonds. We report an electrochemical/chemical exfoliation strategy for synthesizing metal–organic 2D materials based on coordination bonds. A catechol functionalized ligand is used as the redox active pillar to construct a pillared‐layer framework. When the 3D pillared‐layer MOF serves as an electrocatalyst for water oxidation (pH 13), the pillar ligands can be oxidized in situ and removed. The remaining ultrathin (2 nm) nanosheets of the metal–organic layers are an efficient catalyst with overpotentials as low as 211 mV at 10 mA cm−2 and a turnover frequency as high as 30 s−1 at an overpotential of 300 mV.
MOF slicing: A pillared‐layer metal–organic framework (MOF), in which the catechol functionalized pillars can be oxidized and removed in an electrochemical process, gives ultrathin nanosheets (2 nm). These are efficient electrocatalysts for water oxidation at pH 13 with a low overpotential and high turnover frequency (TOF).
Different from previous discrete element methods (DEM), where irregular 3D particle shapes are approximated by subspheres, vertices, or voxels, this study aims to develop an innovative and ...computationally effective DEM method directly employing spherical harmonic functions for simulations of 3D irregular‐shaped particles. First, the discrete surface points of a 3D irregular‐shaped particle are represented by spherical harmonic functions with only a limited number of harmonic coefficients to restore the particle morphology. Then, the intrinsic physical quantities are computed directly using spherical harmonic functions. Next, specific algorithms for interparticle overlapping detection and contact resolution involving the spherical harmonic functions are developed. Subsequently, the interparticle contact forces, moments, and particle movements are computed. The feasibility and capability of the proposed 3D method are verified by simulating random deposition of superellipsoids, repose angle tests, and triaxial tests on particles with various shapes. The proposed method could pave a viable pathway for realistic modeling of granular media pertaining to various engineering and industrial processes.
Human tissue plasminogen activator was the first recombinant therapy protein that successfully produced in Chinese hamster ovary cells in 1986 and approved for clinical use. Since then, more and more ...therapeutic proteins are being manufactured in mammalian cells, and the technologies for recombinant protein production in this expression system have developed rapidly, with the optimization of both upstream and downstream processes. One of the most promising strategies is expression vector cassette optimization based on the expression vector cassette. In this review paper, these approaches and developments are summarized, and the future strategy on the utilizing of expression cassettes for the production of recombinant therapeutic proteins in mammalian cells is discussed.
Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D ...supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial.
Methods
We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D 25(OH)D concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic.
Results
We found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197–0.9988, p = 0.0473, severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699–1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819–1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.
Conclusions
Our MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.
Shape-morphing systems, which can perform complex tasks through morphological transformations, are of great interest for future applications in minimally invasive medicine
, soft robotics
, active ...metamaterials
and smart surfaces
. With current fabrication methods, shape-morphing configurations have been embedded into structural design by, for example, spatial distribution of heterogeneous materials
, which cannot be altered once fabricated. The systems are therefore restricted to a single type of transformation that is predetermined by their geometry. Here we develop a strategy to encode multiple shape-morphing instructions into a micromachine by programming the magnetic configurations of arrays of single-domain nanomagnets on connected panels. This programming is achieved by applying a specific sequence of magnetic fields to nanomagnets with suitably tailored switching fields, and results in specific shape transformations of the customized micromachines under an applied magnetic field. Using this concept, we have built an assembly of modular units that can be programmed to morph into letters of the alphabet, and we have constructed a microscale 'bird' capable of complex behaviours, including 'flapping', 'hovering', 'turning' and 'side-slipping'. This establishes a route for the creation of future intelligent microsystems that are reconfigurable and reprogrammable in situ, and that can therefore adapt to complex situations.
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