Three-Dimensional Printing of a Complex Aortic Anomaly

Complex congenital aortic anomalies include diverse types of malformations that may be clinically asymptomatic or present with respiratory or esophageal ...

Fudan University

Shanghai Institute of Cardiovascular Disease

In polyol synthesis at relatively low concentrations of polyvinylpyrrolidone (PVP, surface-capping agent), some micrometer-size Ag truncated decahedra with five-fold-twinned structure were clearly observed. This result indicates that the internal strain in the five-fold-twinned crystals is not sufficient to restrict their lateral growth. On the basis of first-principles calculation of their surface energies before and after the adsorption of surface-capping agent, it is proposed that the surface energy difference between the (100) and (111) facets (Delta phi(100)-(111)) plays an essential role in the aggressive growth of lateral (100) facets, overcoming the strain restriction. When enough PVP is adsorbed on the surfaces of Ag crystals, the Delta phi(100)-(111) will evidently decrease, and then the strain restriction on the lateral growth becomes predominant, resulting in pentagonal anisotropic structures. Following this mechanism, diameter-tunable Ag wires have been synthesized by controlling the axial growth and the lateral growth separately at higher and lower PVP concentrations, respectively.

Synergy between crystal strain and surface energy in morphological evolution of five-fold-twinned silver crystals.

Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis. 

Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis.

The early warning capability of the presence of biological aerosol threats is an urgent demand in ensuing civilian and military safety. Efficient and rapid air sample collection in relevant indoor or outdoor environment is a key step for subsequent analysis of airborne microorganisms. Herein, we report a portable battery-powered sampler that is capable of highly efficient bioaerosol collection. The essential module of the sampler is a polydimethylsiloxane (PDMS) microfluidic chip, which consisted of a 3-loop double-spiral microchannel featuring embedded herringbone and sawtooth wave-shaped structures. Vibrio parahemolyticus (V. parahemolyticus) as a model microorganism, was initially employed to validate the bioaerosol collection performance of the device. Results showed that the sampling efficacy reached as high as >99.9%. The microfluidic sampler showed greatly improved capturing efficiency compared with traditional plate sedimentation methods. The high performance of our device was attributed to the horizontal inertial centrifugal force and the vertical turbulence applied to airflow during sampling. The centrifugation field and turbulence were generated by the specially designed herringbone structures when air circulated in the double-spiral microchannel. The sawtooth wave-shaped microstructure created larger specific surface area for accommodating more aerosols. Furthermore, a mixture of bacterial aerosols formed by V. parahemolyticus, Listeria monocytogenes, and Escherichia coli was extracted by the microfluidic sampler. Subsequent integration with mass spectrometry conveniently identified the multiple bacterial species captured by the sampler. Our developed stand-alone and cable-free sampler shows clear advantages comparing with conventional strategies, including portability, easy-to-use, and low cost, indicating great potential in future field applications.

Microfluidic Air Sampler for Highly Efficient Bacterial Aerosol Collection and Identification.

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors.

Nanomedicine provides a unique opportunity for promoting drug efficacy through enhanced delivery mechanisms. However, its translation into the clinics has been relatively slow compared with the large amount of research occurring in laboratory settings. Given the limitations of conventional cell culture models and preclinical animal models, we discuss the potential utility of recently developed cancer-on-a-chip platforms, which maximally replicate the pathophysiology of the human tumor microenvironments, as alternatives for effective evaluation of nanomedicine. We begin with a brief discussion of nanomedicine, then chart the history of organ-on-a-chip platform development and their recent evolution as tools for modeling different cancers for assessing nanomedicine efficacy, concluding with future perspectives for the field.

Cancer-on-a-chip systems at the frontier of nanomedicine.

Biochemically modified proteins have attracted significant attention due to their widespread applications as biomaterials. For instance, chemically modified gelatin derivatives have been widely explored to develop hydrogels for tissue engineering and regenerative medicine applications. Among the reported methods, modification of gelatin with methacrylic anhydride (MA) stands out as a convenient and efficient strategy to introduce functional groups and form hydrogels via photopolymerization. Combining light-activation of modified gelatin with soft lithography has enabled the materialization of microfabricated hydrogels. So far, this gelatin derivative has been referred to in the literature as gelatin methacrylate, gelatin methacrylamide, or gelatin methacryloyl, with the same abbreviation of GelMA. Considering the complex composition of gelatin and the presence of different functional groups on the amino acid residues, both hydroxyl groups and amine groups can possibly react with methacrylic anhydride during functionalization of the protein. This can also apply to the modification of other proteins, such as recombinant human tropoelastin to form MA-modified tropoelastin (MeTro). Here, we employed analytical methods to quantitatively determine the amounts of methacrylate and methacrylamide groups in MA-modified gelatin and tropoelastin to better understand the reaction mechanism. By combining two chemical assays with instrumental techniques, such as proton nuclear magnetic resonance ((1)H NMR) and liquid chromatography tandem-mass spectrometry (LC-MS/MS), our results indicated that while amine groups had higher reactivity than hydroxyl groups and resulted in a majority of methacrylamide groups, modification of proteins by MA could lead to the formation of both methacrylamide and methacrylate groups. It is therefore suggested that the standard terms for GelMA and MeTro should be defined as gelatin methacryloyl and methacryloyl-substituted tropoelastin, respectively, to remain consistent with the widespread abbreviations used in literature.

Structural analysis of photocrosslinkable methacryloyl-modified protein derivatives.

Method development for monitoring economically motivated food adulteration is pivotal for preventing health problems caused by illegal food additives. In this work, low-field nuclear magnetic resonance (LF-NMR) spectroscopy and magnetic resonance imaging (MRI) was applied for the detection and mapping of adulterated prawns injected with different hydrocolloids including gelatin, carrageenan, agar, amorophophallus konjac and xanthan gum. The characteristic T fitting curves were obtained which can be used to tell apart adulterated prawns from normal ones. Furthermore, the benefit from high quality LF-MRI images showed the major accumulation site of the hydrocolloids injected in prawn. The location of these injections was mainly confined to well resolved accumulation in brain region and three following subtle sites: back, tail and claws. Different hydrocolloids can be successfully distinguished in adulterated prawns with principal component analysis. Therefore, rapid, non-invasive and low-cost LF-NMR technique offers a powerful tool for the identification of hydrocolloids adulteration in real-time.

Rapid and non-invasive detection and imaging of the hydrocolloid-injected prawns with low-field NMR and MRI.

Conducting hydrogels provide great potential for creating designer shape-morphing architectures for biomedical applications owing to their unique solid-liquid interface and ease of processability. Here, a novel nanofibrous hydrogel with significant enzyme-like activity that can be used as "ink" to print flexible electrochemical devices is developed. The nanofibrous hydrogel is self-assembled from guanosine (G) and KB(OH) with simultaneous incorporation of hemin into the G-quartet scaffold, giving rise to significant enzyme-like activity. The rapid switching between the sol and gel states responsive to shear stress enables free-form fabrication of different patterns. Furthermore, the replication of the G-quartet wires into a conductive matrix by in situ catalytic deposition of polyaniline on nanofibers is demonstrated, which can be directly printed into a flexible electrochemical electrode. By loading glucose oxidase into this novel hydrogel, a flexible glucose biosensor is developed. This study sheds new light on developing artificial enzymes with new functionalities and on fabrication of flexible bioelectronics.

Self-Assembly of Enzyme-Like Nanofibrous G-Molecular Hydrogel for Printed Flexible Electrochemical Sensors.

Protein glycosylation is a significant participant in a mass of biological processes, which is a pivotal protein post-translational modification. Due to the low contents of glycopeptides compared with nonglycopeptides and the microheterogeneity of glycosylation sites, highly selective enrichment methods for the purification of glycopeptides are required for the comprehensive characterization of glycoproteomics. In this work, a type of magnetic mesoporous phenolic resin (MMP) was prepared using branched polyethylenimine (PEI) as a cross-linker from a homogeneous magnetic FeO@SiO solution in a resorcinol/formaldehyde monomer aqueous system via an in situ emulsion polymerization procedure. The results showed that MMP exhibited good biocompatibility, a mesoporous structure, nitrogen-containing functionality, excellent hydrophilicity, and solvent resistance by using multiple characterization methods. By taking advantage of the interaction between hydrophilic groups on the MMP and glycan components on the glycopeptides, the acquired MMP was utilized to the selective capture of N-glycopeptides (human IgG or HRP tryptic digests/BSA proteins = 1:50), good recovery yield (70.18-97.23%), superior binding capacity (400 mg g), and excellent reproducibility. Based on the outstanding performance in standard glycoproteins tryptic digests enrichment, MMP was further used to capture N-glycopeptides from tryptic digests of human serum. A total of 15 unique N-glycopeptides were identified from an ultralow sample volume (0.025 μL) of human serum. Overall, we identified 356 unique N-glycopeptides corresponding to 119 glycoproteins from human serum (0.35 μL) in the overlap of three replicate analyses. All the results have demonstrated that MMP has great potential in large-scale N-glycoproteomics research.

In Situ Synthesis of Magnetic Mesoporous Phenolic Resin for the Selective Enrichment of Glycopeptides.

The recently developed 3D bioprinting technology has greatly improved the ability to generate biomimetic tissues that are structurally and functionally relevant to their human counterparts. The selection of proper biomaterials as the bioinks is a key step toward successful bioprinting. For example, viscosity of a bioink is an important rheological parameter to determine the flexibility in deposition of free-standing structures and the maintenance of architectural integrity following bioprinting. This requirement, however, has greatly limited the selection of bioinks, especially for those naturally derived due to their commonly low mechanical properties. Here the generalization of a mechanism for extrusion bioprinting of bio-macromolecular components, mainly focusing on collagen and its derivatives including gelatin and gelatin methacryloyl, is reported. Specifically, a templating strategy is adopted using a composite bioink containing both the desired bio-macromolecular component and a polysaccharide alginate. The physically crosslinkable alginate component serves as the temporal structural support to stabilize the shape of the construct during bioprinting; upon subsequent chemical or physical crosslinking of the bio-macromolecular component, alginate can be selectively removed to leave only the desired bio-macromolecule. It is anticipated that this strategy is general, and can be readily expanded for use of a wide variety of other bio-macromolecular bioinks.

Weijia Zhang

Department of Cardiac Surgery,
Zhongshan Hospital,
State Key Laboratory of Molecular Engineering of Polymers,
Institutes of Biomedical Sciences,
Department of Cardiac Surgery, Zhongshan Hospital

Fudan University

Three-Dimensional Printing of a Complex Aortic Anomaly

Weijia Zhang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Cardiac Surgery,Zhongshan Hospital,State Key Laboratory of Molecular Engineering of Polymers,Institutes of Biomedical Sciences,Department of Cardiac Surgery, Zhongshan Hospital

Fudan University

Three-Dimensional Printing of a Complex Aortic Anomaly

Department of Cardiac Surgery,
Zhongshan Hospital,
State Key Laboratory of Molecular Engineering of Polymers,
Institutes of Biomedical Sciences,
Department of Cardiac Surgery, Zhongshan Hospital