Repeat it without me: Crowdsourcing the T1 mapping common ground via the ISMRM reproducibility challenge.

PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.

Lung parenchyma transverse relaxation rates at 0.55 T.

PURPOSE: To determine R2 and R 2 ' $$ {R}_2^{\prime } $$ transverse relaxation rates in healthy lung parenchyma at 0.55 T. This is important in that it informs the design and optimization of new imaging methods for 0.55T lung MRI. METHODS: Experiments were performed in 3 healthy adult volunteers on a prototype whole-body 0.55T MRI, using a custom free-breathing electrocardiogram-triggered, single-slice echo-shifted multi-echo spin echo (ES-MCSE) pulse sequence with respiratory navigation. Transverse relaxation rates R2 and R 2 ' $$ {R}_2^{\prime } $$ and off-resonance ∆f were jointly estimated using nonlinear least-squares estimation. These measurements were compared against R2 estimates from T2 -prepared balanced SSFP (T2 -Prep bSSFP) and R 2 * $$ {R}_2^{\ast } $$ estimates from multi-echo gradient echo, which are used widely but prone to error due to different subvoxel weighting. RESULTS: The mean R2 and R 2 ' $$ {R}_2^{\prime } $$ values of lung parenchyma obtained from ES-MCSE were 17.3 ± 0.7 Hz and 127.5 ± 16.4 Hz (T2  = 61.6 ± 1.7 ms; T 2 ' $$ {\mathrm{T}}_2^{\prime } $$  = 9.5 ms ± 1.6 ms), respectively. The off-resonance estimates ranged from -60 to 30 Hz. The R2 from T2 -Prep bSSFP was 15.7 ± 1.7 Hz (T2  = 68.6 ± 8.6 ms) and R 2 * $$ {R}_2^{\ast } $$ from multi-echo gradient echo was 131.2 ± 30.4 Hz ( T 2 * $$ {\mathrm{T}}_2^{\ast } $$  = 8.0 ± 2.5 ms). Paired t-test indicated that there is a significant difference between the proposed and reference methods (p < 0.05). The mean R2 estimate from T2 -Prep bSSFP was slightly smaller than that from ES-MCSE, whereas the mean R 2 ' $$ {R}_2^{\prime } $$ and R 2 * $$ {R}_2^{\ast } $$ estimates from ES-MCSE and multi-echo gradient echo were similar to each other across all subjects. CONCLUSIONS: Joint estimation of transverse relaxation rates and off-resonance is feasible at 0.55 T with a free-breathing electrocardiogram-gated and navigator-gated ES-MCSE sequence. At 0.55 T, the mean R2 of 17.3 Hz is similar to the reported mean R2 of 16.7 Hz at 1.5 T, but the mean R 2 ' $$ {R}_2^{\prime } $$ of 127.5 Hz is about 5-10 times smaller than that reported at 1.5 T.

A geometric view of signal sensitivity metrics in multi-echo fMRI.

In multi-echo fMRI (ME-fMRI), two metrics have been widely used to measure the performance of various acquisition and analysis approaches. These are temporal SNR (tSNR) and differential contrast-to-noise ratio (dCNR). A key step in ME-fMRI is the weighted combination of the data from multiple echoes, and prior work has examined the dependence of tSNR and dCNR on the choice of weights. However, most studies have focused on only one of these two metrics, and the relationship between the two metrics has not been examined. In this work, we present a geometric view that offers greater insight into the relation between the two metrics and their weight dependence. We identify three major regimes: (1) a tSNR robust regime in which tSNR is robust to the weight selection with most weight variants achieving close to optimal performance, whereas dCNR shows a pronounced dependence on the weights with most variants achieving suboptimal performance; (2) a dCNR robust regime in which dCNR is robust to the weight selection with most weight variants achieving close to optimal performance, while tSNR exhibits a strong dependence on the weights with most variants achieving significantly lower than optimal performance; and (3) a within-type robust regime in which both tSNR and dCNR achieve nearly optimal performance when the form of the weights are variants of their respective optimal weights and exhibit a moderate decrease in performance for other weight variants. Insight into the behavior observed in the different regimes is gained by considering spherical representations of the weight dependence of the components used to form each metric. For multi-echo acquisitions, dCNR is shown to be more directly related than tSNR to measures of CNR and signal-to-noise ratio (SNR) for task-based and resting-state fMRI scans, respectively.

Probing Herbicide Toxicity to Algae (Selenastrum capricornutum) by Lipid Profiling with Machine Learning and Microchip/MALDI-TOF Mass Spectrometry.

Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS)-based lipid profiling is a powerful method to study the cytotoxicity of chemical exposure to microorganisms at the single cell level. We report here a combined approach of machine learning (ML) and microchip-based MALDI-time of flight (TOF) mass spectrometry to investigate the cytotoxic effect of herbicides on algae through single cell lipid profiling. Algal species Selenastrum capricornutum was chosen as the target system, and its exposure to different doses of common chemical herbicides and the resulting cytotoxic behaviors under various stress conditions were characterized. A lipid library for S. capricornutum has been established with 63 identified lipids that include glycosyldiacylglycerols and triacylglycerols. We demonstrated that major alternations occurred for lipids with functional groups of digalactosyldiacylglycerol (DGDG), triacylglycerol (TAG), and monogalactosyldiacylglycerol (MGDG). DGDG was shown to decrease upon exposure to herbicides of norflurazon and atrazine, while some MGDG and TAG lipids would increase for norflurazon. Compared to other algae, S. capricornutum was more strongly impacted by norflurazon than atrazine while the latter was observed to have a greater effect on C. reinhardtii. Machine learning algorithms have been applied to improve the classification of herbicide impact and help identify lipid species affected by the chemical exposure. A total of 69 machine learning models were trained and tested for the identification of ideal algorithms in the classification process, in which flexible discriminant analysis and support vector machine model were found to be the most accurate and consistent. The ML algorithms accurately differentiated herbicide impact and have identified cytotoxic differences that were previously hidden. The results suggest that herbicides express toxicity among different algae likely on the basis of metabolic differences. The ML-assisted method proves to be highly effective and can provide an advanced technological platform for probing cytotoxicity for bacterial species and in metabolic pathway analysis.

Lipidomic Profiling of Algae with Microarray MALDI-MS toward Ecotoxicological Monitoring of Herbicide Exposure.

Misuse of agrochemicals has a long-lasting negative impact on aquatic systems. Mismanagement of herbicides in agri-food sectors is often linked to a simultaneous decline in the health of downstream waterways. However, monitoring the herbicide levels in these areas is a laborious task, and modern analytical approaches, such as solid-phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) and enzyme-linked immunosorbent assay, are low-throughput and require significant sample preparation. We report here the use of microchip technology in combination with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) for the assessment of the ecotoxicological effect of agrochemicals on aquatic species at the single-cell level. This approach quantifies the fluctuations in lipid content in sentinel organisms and targets the microalga, Chlamydomonas reinhardtii (C. reinhardtii), as the model system. Specifically, we investigated the cytotoxicity of three herbicides (atrazine, clomazone, and norflurazon) on C. reinhardtii by analyzing the lipid component variation upon assorted herbicide exposure. Lipidomic profiling reveals a significantly altered lipid content at >EC50 in atrazine-exposed cells. The response for norflurazon showed similar trends but diminished in magnitude, while the result for clomazone was near muted. At lower herbicide concentrations, digalactosyldiacylglycerols showed a rapid decrease in abundance, while several other lipids displayed a moderate increase. The microchip-based MALDI technique demonstrates the ability to achieve lipidomic profiling of aquatic species exposed to different stressors, proving effective for high-throughput screening and single-cell analysis in ecotoxicity studies.

Detection of Multiple Sclerosis Biomarkers in Serum by Ganglioside Microarrays and Surface Plasmon Resonance Imaging.

Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheaths of nerve cells in the central nervous system. An individual suffering from MS produces increased levels of antibodies that target cell membrane components, such as phospholipids, gangliosides, and membrane proteins. Among them, anti-ganglioside antibodies are considered as important biomarkers to differentiate MS from other diseases that exhibit similar symptoms. We report here a label-free method for detecting a series of antibodies against gangliosides in serum by surface plasmon resonance imaging (SPRi) in combination with a carbohydrate microarray. The ganglioside array was fabricated with a plasmonically tuned, background-free biochip, and coated with a perfluorodecyltrichlorosilane (PFDTS) layer for antigen attachment as a self-assembled pseudo-myelin sheath. The chip was characterized with AFM and matrix-assisted laser desorption ionization mass spectrometry, demonstrating effective functionalization of the surface. SPRi measurements of patients' mimicking blood samples were conducted. A multiplexed detection of antibodies for anti-GT1b, anti-GM1, and anti-GA1 in serum was demonstrated, with a working range of 1 to 100 ng/mL, suggesting that it is well suited for clinical assessment of antibody abnormality in MS patients. Statistical analyses, including PLS-DA and PCA show the array allows comprehensive characterization of cross reactivity patterns between the MS specific antibodies and can generate a wide range of information compared to traditional end point assays. This work uses PFDTS surface functionalization and enables direct MS biomarker detection in serum, offering a powerful alternative for MS assessment and potentially improved patient care.

Exercise MRI highlights heterogeneity in cardiovascular mechanics among patients with Fontan circulation: proposed protocol for routine evaluation.

Single ventricle physiology and palliation via the Fontan operation lead to a series of cardiovascular changes. In addition, organs such as the kidneys and liver have been shown to experience insults and subsequent injury. This has led to routine surveillance of patients. We present findings from a small cohort of patients that was deeply phenotyped to illustrate the need for comprehensive evaluation. A cohort of four Fontan patients with fairly high cardiovascular function was recruited 5-10 years post-Fontan. Patients underwent a rigorous clinical work-up after which a research MRI scan was performed during which (I) data were obtained during exercise to evaluate changes in stroke volume during supine exercise and (II) magnetic resonance angiograms with phase-contrast images were obtained for computational modeling of flows through the Fontan circulation at rest. Clinical measures were consistent with a fairly homogeneous high function cohort (peak oxygen consumption >20 mL/kg/min, robust response to exercise, peak ventilatory efficiency below levels associated with heart failure, MR-derived ejection fraction >50%). Liver evaluation did not reveal clear signs of cirrhosis or extensive fibrosis. However, we observed considerable variability (27-162%) in the increase in stroke index with exercise [100%±64% increase, 53.9±17.4 mL/beat m2 (rest), 101.1±20.7 mL/beat m2, (exercise)]. Computational flow modeling at rest in two patients also showed marked differences in flow distribution and shear stress. We report marked differences in both changes in stroke index during an exercise MRI protocol as well as computational flow patterns at rest suggesting different compensation strategies may be associated with high functioning Fontan patients. The observed heterogeneity illustrates the need for deep phenotyping to capture patient-specific adaptive mechanisms.

Plasmonic Gold Templates Enhancing Single Cell Lipidomic Analysis of Microorganisms.

Single cell lipid profiling is a powerful tool to connect membrane composition and its changes within individual cells to specific biochemical functions or stimuli, but current approaches are inadequate due to the complex nature of the cells and technical limitation in analysis. Herein we report a new method with plasmonic substrates capable of cell localization and enhanced lipid ionization through thin-gold-film MALDI-MS. We performed lipidomic profiling of algae single cells with a 120-well microarray and identified more than 50 lipids in C. reinhardtii without an extraction process. The substrate was used for probing toxicological effect of herbicide atrazine on the algae's lipidome, demonstrating molecular changes in glycerol lipid profiles. Fast location of cells with metal-enhanced fluorescence (MEF) and subsequent precise and direct ionization of the LDI process contribute to the enhanced performance, allowing for assessment of lipid changes concurrent with atrazine affected populations. This method that combines microarrays, MEF, and MALDI-MS presents an effective platform for lipidomic study of single cells and for environmental toxicity study with microorganisms.

Photothermal-assisted surface-mediated gene delivery for enhancing transfection efficiency.

The development of gene therapy puts forward the requirements for efficient delivery of genetic information into diverse cells. However, in some cases of transfection, especially those for transfecting some primary cells and for delivering large size plasmid DNA (pDNA), the existing conventional transfection methods show poor efficiency. How to further improve transfection efficiency in these hard-to-achieve issues remains a crucial challenge. Here, we report a photothermal-assisted surface-mediated gene delivery based on a polydopamine-polyethylenimine (PDA-PEI) surface. The PDA-PEI surface was prepared through PEI-accelerated dopamine polymerization, which showed efficiency in the immobilization of PEI/pDNA polyplexes and remarkable photothermal properties. Upon IR irradiation, we observed improved transfection efficiencies of two important hard-to-achieve transfection issues, namely the transfection of primary endothelial cells, which are kinds of typical hard-to-transfect cells, and the transfection of cells with large-size pDNA. We demonstrate that the increases of transfection efficiency were due to the hyperthermia-induced pDNA release, the local cell membrane disturbance, and the polyplex internalization. This work highlights the importance of local immobilization and release of pDNA to gene deliveries, showing great potential applications in medical devices in the field of gene therapy.

Photothermal Killing of Methicillin-Resistant Staphylococcus aureus by Bacteria-Targeted Polydopamine Nanoparticles with Nano-Localized Hyperpyrexia.

Bacterial infections caused by antibiotic-resistant pathogens have become intractable problems to public health. Therefore, there is an imperious demand for developing new approaches to effectively kill antibiotic-resistant bacteria. In this work, we report a kind of bacteria-targeted polydopamine nanoparticle exhibiting great photothermal killing ability toward methicillin-resistant Staphylococcus aureus (MRSA) by nano-localized hyperpyrexia under low-power near-infrared (NIR) light irradiation. These bacteria-targeted nanoparticles (PDA-PEG-Van) are prepared by modifying polydopamine nanoparticles with thiol-poly(ethylene glycol) (mPEG-SH) and vancomycin (Van) molecules. The PEG shell endows the nanoparticles with excellent long-term circulation stability. Due to the multivalent hydrogen-bond interactions between vancomycin and the MRSA cell wall, the vancomycin-modified polydopamine nanoparticles can specifically target MRSA rather than mammalian cells. These bacteria-targeted nanoparticles are employed as a nano-localized heat source to kill MRSA via disrupting the bacterial cell wall and membrane under irradiation of low-power NIR light. More importantly, the surrounding healthy tissues suffer bare damage, owing to the absence of any targeting effect of PDA-PEG-Van toward mammalian cells and the low power of NIR light used in the therapeutic process. Given the above advantages, the bacteria-targeted polydopamine nanoparticles proposed in this work show tremendous potential to treat MRSA infections, because they can effectively limit localized heating in the infection sites to kill bacteria and cut down damage to healthy tissues.

Improved Antithrombotic Function of Oriented Endothelial Cell Monolayer on Microgrooves.

Achievement of an endothelial cell (EC) monolayer (re-endothelialization) on the vascular implant surface with competent and functioning features is critical for long-term safety after implantation. Oriented EC monolayer is beneficial to improve endothelial function such as enhanced athero-resistant property. However, the information about antithrombotic property of oriented EC monolayer is limited. Here, we used the microgrooved polydimethylsiloxane substrates to guide EC orientation and obtain oriented EC monolayer. The effects of anisotropic topography on EC behaviors and antithrombotic function of the EC monolayer were then evaluated. Our data demonstrated that ECs responded to grooves in a size-dependent way as shown in oriented cell cytoskeleton and nuclei, enhanced directed migration, and overall velocity. Furthermore, compared to the EC monolayer on the flat surface, the oriented EC monolayer formed on the grooved substrates exhibited improved antithrombotic capability as indicated by higher expression of functional related genes, production of prostacyclin and tissue plasminogen activator, and prolonged activated coagulation time. The improvement of antithrombotic function was especially notable on the smaller-size groove. These findings reveal the responses of ECs to varisized topography and antithrombotic function of the oriented EC monolayer, providing insights into optimal design of vascular implants.

Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip.

Organic-Inorganic Copper(II)-Based Material: A Low-Toxic, Highly Stable Light Absorber for Photovoltaic Application.

Lead halide perovskite solar cells have recently emerged as a very promising photovoltaic technology due to their excellent power conversion efficiencies; however, the toxicity of lead and the poor stability of perovskite materials remain two main challenges that need to be addressed. Here, for the first time, we report a lead-free, highly stable C6H4NH2CuBr2I compound. The C6H4NH2CuBr2I films exhibit extraordinary hydrophobic behavior with a contact angle of ∼90°, and their X-ray diffraction patterns remain unchanged even after 4 h of water immersion. UV/vis absorption spectrum shows that C6H4NH2CuBr2I compound has an excellent optical absorption over the entire visible spectrum. We applied this copper-based light absorber in printable mesoscopic solar cell for the initial trial and achieved a power conversion efficiency of ∼0.5%. Our study represents an alternative pathway to develop low-toxic and highly stable organic-inorganic hybrid materials for photovoltaic application.

Spatial Abundance, Diversity, and Activity of Ammonia-Oxidizing Bacteria in Coastal Sediments of the Liaohe Estuary.

Ammonia-oxidizing bacteria (AOB) play an important role in nitrification in estuaries. The aim of this study was to examine the spatial abundance, diversity, and activity of AOB in coastal sediments of the Liaohe Estuary using quantitative PCR, high-throughput sequencing of the amoA gene coding the ammonia monooxygenase enzyme active subunit, and sediment slurry incubation experiments. AOB abundance ranged from 8.54 × 104 to 5.85 × 106 copies g-1 of wet sediment weight and exhibited an increasing trend from the Liaohe Estuary to the open coastal zone. Potential nitrification rates (PNRs) ranged from 0.1 to 336.8 nmol N g-1 day-1 along the estuary to the coastal zone. Log AOB abundance and PNRs were significantly positively correlated. AOB richness decreased from the estuary to the coastal zone. High-throughput sequencing analysis indicated that the majority of amoA gene sequences fell within the Nitrosomonas and Nitrosomonas-like clade, and only a few sequences were clustered within the Nitrosospira clade. This finding indicates that the Nitrosomonas-related lineage may be more adaptable to the specific conditions in this estuary than the Nitrosospira lineage. Sites with high nitrification rates were located in the southern open region and were dominated by the Nitrosomonas-like lineage, whereas the Nitrosospira lineage was found primarily in the northern estuary mouth sites with low nitrification rates. Thus, nitrification potentials in Liaohe estuarine sediments in the southern open region were greater than those in the northern estuary mouth, and the Nitrosomonas-related lineage might play a more important role than the Nitrosospira lineage in nitrification in this estuary.

The Preparation and Properties Study of High CRI White LED Based on Remote Phosphor Technology.

Focusing on the defects in the lighting color of LED lamps and the chip heat exists in the traditional LED package which caused phosphor performance degradation, color temperature drift and the uneven light, the remote phosphor package which is emerging in recent years is used in this paper. With yellow-green YGG phosphor and nitrogen red phosphors mixing with silica gel, the remote phosphor is made and then encapsulated as the LED lamps. A lot of experiments were made to determine the best ratio of yellow green phosphor, red phosphor and silica gel, LED lamps with different color temperature was prepared. The lamps were also tested and analyzed with some parameters such as e color coordinates, luminous efficiency, color rendering index (CRI), R9, color quality scale (CQS), color temperature, and the gamut area index (GAI), which provide a more objective and comprehensive evaluation to the high quality LED lighting. Experimental results show that the optimum ratio of red and yellow-green phosphor is 1∶7.6, and total phosphor with silica gel is 1∶5，at this time the white LED lighting color temperature is 4 113 K, the color coordinate (x, y) is (0.375 4, 0.373 1), luminous efficiency is 52.33 lm·w-1, color gamut is 0.981, color rendering index is up to 96, R9 is 97, color quality scale Qa is up to 93, and the gamut area index is 79. Compared with the traditional packaging，the surface temperature ofthe remote phosphor encapsulated fluorescent plate is much lower than that of adhesive dispensing encapsulation, which can effectively avoid the harmful effect caused by high temperature on the LED.

Stiffness of polyelectrolyte multilayer film influences endothelial function of endothelial cell monolayer.

Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.

Substrate-mediated delivery of gene complex nanoparticles via polydopamine coating for enhancing competitiveness of endothelial cells.

Substrate-mediated delivery of functional plasmid DNA (pDNA) has been proven to be a promising strategy to promote competitiveness of endothelial cells (ECs) over smooth muscle cells (SMCs), which is beneficial to inducing fast endothelialization of implanted vascular devices. Thus, it is of great importance to develop universal approaches with simplicity and easiness to immobilize DNA complex nanoparticles on substrates. In this study, the bioinspired polydopamine (PDA) coating was employed in immobilization of DNA complex nanoparticles, which were composed of protamine (PrS) and plasmid DNA encoding with hepatocyte growth factor (HGF-pDNA) gene. We demonstrated that the DNA complex nanoparticles can be successfully immobilized onto the PDA surface. Consequently, the HGF expression of both ECs and SMCs were significantly improved when they cultured on the DNA complex nanoparticles-immobilized substrates. Furthermore, EC proliferation was specifically promoted due to bioactivity of HGF, leading to an enhancement of EC competitiveness over SMCs. Our findings demonstrated the substrate-mediated functional gene nanoparticle delivery through PDA coating as a simple and efficient approach. It may hold great potential in the field of interventional cardiovascular implants.

Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.

Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC-based regenerative medicine.

Improved Endothelial Function of Endothelial Cell Monolayer on the Soft Polyelectrolyte Multilayer Film with Matrix-Bound Vascular Endothelial Growth Factor.

Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.

Layer-by-layer-assembled healable antifouling films.

Healable antifouling films are fabricated by the exponential layer-by-layer assembly of PEGylated branched poly(ethylenimine) and hyaluronic acid followed by post-crosslinking. The antifouling function originates from the grafted PEG and the extremely soft nature of the films. The rapid and multiple healing of damaged antifouling functions caused by cuts and scratches can be readily achieved by immersing the films in normal saline solution.