Instant tough adhesion of polymer networks.

Generating strong rapid adhesion between hydrogels has the potential to advance the capabilities of modern medicine and surgery. Current hydrogel adhesion technologies rely primarily on liquid-based diffusion mechanisms and the formation of covalent bonds, requiring prolonged time to generate adhesion. Here, we present a simple and versatile strategy using dry chitosan polymer films to generate instant adhesion between hydrogel-hydrogel and hydrogel-elastomer surfaces. Using this approach we can achieve extremely high adhesive energies (>3,000 J/m2), which are governed by pH change and non-covalent interactions including H-bonding, Van der Waals forces, and bridging polymer entanglement. Potential examples of biomedical applications are presented, including local tissue cooling, vascular sealing, prevention of surgical adhesions, and prevention of hydrogel dehydration. We expect these findings and the simplicity of this approach to have broad implications for adhesion strategies and hydrogel design.

Ultra-sensitive and resilient compliant strain gauges for soft machines.

Soft machines are a promising design paradigm for human-centric devices1,2 and systems required to interact gently with their environment3,4. To enable soft machines to respond intelligently to their surroundings, compliant sensory feedback mechanisms are needed. Specifically, soft alternatives to strain gauges-with high resolution at low strain (less than 5 per cent)-could unlock promising new capabilities in soft systems. However, currently available sensing mechanisms typically possess either high strain sensitivity or high mechanical resilience, but not both. The scarcity of resilient and compliant ultra-sensitive sensing mechanisms has confined their operation to laboratory settings, inhibiting their widespread deployment. Here we present a versatile and compliant transduction mechanism for high-sensitivity strain detection with high mechanical resilience, based on strain-mediated contact in anisotropically resistive structures (SCARS). The mechanism relies upon changes in Ohmic contact between stiff, micro-structured, anisotropically conductive meanders encapsulated by stretchable films. The mechanism achieves high sensitivity, with gauge factors greater than 85,000, while being adaptable for use with high-strength conductors, thus producing sensors resilient to adverse loading conditions. The sensing mechanism also exhibits high linearity, as well as insensitivity to bending and twisting deformations-features that are important for soft device applications. To demonstrate the potential impact of our technology, we construct a sensor-integrated, lightweight, textile-based arm sleeve that can recognize gestures without encumbering the hand. We demonstrate predictive tracking and classification of discrete gestures and continuous hand motions via detection of small muscle movements in the arm. The sleeve demonstration shows the potential of the SCARS technology for the development of unobtrusive, wearable biomechanical feedback systems and human-computer interfaces.

Carbon-cement supercapacitors as a scalable bulk energy storage solution.

The large-scale implementation of renewable energy systems necessitates the development of energy storage solutions to effectively manage imbalances between energy supply and demand. Herein, we investigate such a scalable material solution for energy storage in supercapacitors constructed from readily available material precursors that can be locally sourced from virtually anywhere on the planet, namely cement, water, and carbon black. We characterize our carbon-cement electrodes by combining correlative EDS-Raman spectroscopy with capacitance measurements derived from cyclic voltammetry and galvanostatic charge-discharge experiments using integer and fractional derivatives to correct for rate and current intensity effects. Texture analysis reveals that the hydration reactions of cement in the presence of carbon generate a fractal-like electron-conducting carbon network that permeates the load-bearing cement-based matrix. The energy storage capacity of this space-filling carbon black network of the high specific surface area accessible to charge storage is shown to be an intensive quantity, whereas the high-rate capability of the carbon-cement electrodes exhibits self-similarity due to the hydration porosity available for charge transport. This intensive and self-similar nature of energy storage and rate capability represents an opportunity for mass scaling from electrode to structural scales. The availability, versatility, and scalability of these carbon-cement supercapacitors opens a horizon for the design of multifunctional structures that leverage high energy storage capacity, high-rate charge/discharge capabilities, and structural strength for sustainable residential and industrial applications ranging from energy autarkic shelters and self-charging roads for electric vehicles, to intermittent energy storage for wind turbines and tidal power stations.

Active entanglement enables stochastic, topological grasping.

Grasping, in both biological and engineered mechanisms, can be highly sensitive to the gripper and object morphology, as well as perception and motion planning. Here, we circumvent the need for feedback or precise planning by using an array of fluidically actuated slender hollow elastomeric filaments to actively entangle with objects that vary in geometric and topological complexity. The resulting stochastic interactions enable a unique soft and conformable grasping strategy across a range of target objects that vary in size, weight, and shape. We experimentally evaluate the grasping performance of our strategy and use a computational framework for the collective mechanics of flexible filaments in contact with complex objects to explain our findings. Overall, our study highlights how active collective entanglement of a filament array via an uncontrolled, spatially distributed scheme provides options for soft, adaptable grasping.

Microstructural design for mechanical-optical multifunctionality in the exoskeleton of the flower beetle Torynorrhina flammea.

Biological systems have a remarkable capability of synthesizing multifunctional materials that are adapted for specific physiological and ecological needs. When exploring structure-function relationships related to multifunctionality in nature, it can be a challenging task to address performance synergies, trade-offs, and the relative importance of different functions in biological materials, which, in turn, can hinder our ability to successfully develop their synthetic bioinspired counterparts. Here, we investigate such relationships between the mechanical and optical properties in a multifunctional biological material found in the highly protective yet conspicuously colored exoskeleton of the flower beetle, Torynorrhina flammea Combining experimental, computational, and theoretical approaches, we demonstrate that a micropillar-reinforced photonic multilayer in the beetle's exoskeleton simultaneously enhances mechanical robustness and optical appearance, giving rise to optical damage tolerance. Compared with plain multilayer structures, stiffer vertical micropillars increase stiffness and elastic recovery, restrain the formation of shear bands, and enhance delamination resistance. The micropillars also scatter the reflected light at larger polar angles, enhancing the first optical diffraction order, which makes the reflected color visible from a wider range of viewing angles. The synergistic effect of the improved angular reflectivity and damage localization capability contributes to the optical damage tolerance. Our systematic structural analysis of T. flammea's different color polymorphs and parametric optical and mechanical modeling further suggest that the beetle's microarchitecture is optimized toward maximizing the first-order optical diffraction rather than its mechanical stiffness. These findings shed light on material-level design strategies utilized in biological systems for achieving multifunctionality and could thus inform bioinspired material innovations.

High-throughput segmentation, data visualization, and analysis of sea star skeletal networks.

The remarkably complex skeletal systems of the sea stars (Echinodermata, Asteroidea), consisting of hundreds to thousands of individual elements (ossicles), have intrigued investigators for more than 150 years. While the general features and structural diversity of isolated asteroid ossicles have been well documented in the literature, the task of mapping the spatial organization of these constituent skeletal elements in a whole-animal context represents an incredibly laborious process, and as such, has remained largely unexplored. To address this unmet need, particularly in the context of understanding structure-function relationships in these complex skeletal systems, we present an integrated approach that combines micro-computed tomography, automated ossicle segmentation, data visualization tools, and the production of additively manufactured tangible models to reveal biologically relevant structural data that can be rapidly analyzed in an intuitive manner. In the present study, we demonstrate this high-throughput workflow by segmenting and analyzing entire skeletal systems of the giant knobby star, Pisaster giganteus, at four different stages of growth. The in-depth analysis, presented herein, provides a fundamental understanding of the three-dimensional skeletal architecture of the sea star body wall, the process of skeletal maturation during growth, and the relationship between skeletal organization and morphological characteristics of individual ossicles. The widespread implementation of this approach for investigating other species, subspecies, and growth series has the potential to fundamentally improve our understanding of asteroid skeletal architecture and biodiversity in relation to mobility, feeding habits, and environmental specialization in this fascinating group of echinoderms.

Rational design of reconfigurable prismatic architected materials.

Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in this way to enable tunable functionality. Inspired by the structural diversity and foldability of the prismatic geometries that can be constructed using the snapology origami technique, here we introduce a robust design strategy based on space-filling tessellations of polyhedra to create three-dimensional reconfigurable materials comprising a periodic assembly of rigid plates and elastic hinges. Guided by numerical analysis and physical prototypes, we systematically explore the mobility of the designed structures and identify a wide range of qualitatively different deformations and internal rearrangements. Given that the underlying principles are scale-independent, our strategy can be applied to the design of the next generation of reconfigurable structures and materials, ranging from metre-scale transformable architectures to nanometre-scale tunable photonic systems.

Mechanically robust lattices inspired by deep-sea glass sponges.

The predominantly deep-sea hexactinellid sponges are known for their ability to construct remarkably complex skeletons from amorphous hydrated silica. The skeletal system of one such species of sponge, Euplectella aspergillum, consists of a square-grid-like architecture overlaid with a double set of diagonal bracings, creating a chequerboard-like pattern of open and closed cells. Here, using a combination of finite element simulations and mechanical tests on 3D-printed specimens of different lattice geometries, we show that the sponge's diagonal reinforcement strategy achieves the highest buckling resistance for a given amount of material. Furthermore, using an evolutionary optimization algorithm, we show that our sponge-inspired lattice geometry approaches the optimum material distribution for the design space considered. Our results demonstrate that lessons learned from the study of sponge skeletal systems can be exploited for the realization of square lattice geometries that are geometrically optimized to avoid global structural buckling, with implications for improved material use in modern infrastructural applications.

Condensation on slippery asymmetric bumps.

Controlling dropwise condensation is fundamental to water-harvesting systems, desalination, thermal power generation, air conditioning, distillation towers, and numerous other applications. For any of these, it is essential to design surfaces that enable droplets to grow rapidly and to be shed as quickly as possible. However, approaches based on microscale, nanoscale or molecular-scale textures suffer from intrinsic trade-offs that make it difficult to optimize both growth and transport at once. Here we present a conceptually different design approach--based on principles derived from Namib desert beetles, cacti, and pitcher plants--that synergistically combines these aspects of condensation and substantially outperforms other synthetic surfaces. Inspired by an unconventional interpretation of the role of the beetle's bumpy surface geometry in promoting condensation, and using theoretical modelling, we show how to maximize vapour diffusion fluxat the apex of convex millimetric bumps by optimizing the radius of curvature and cross-sectional shape. Integrating this apex geometry with a widening slope, analogous to cactus spines, directly couples facilitated droplet growth with fast directional transport, by creating a free-energy profile that drives the droplet down the slope before its growth rate can decrease. This coupling is further enhanced by a slippery, pitcher-plant-inspired nanocoating that facilitates feedback between coalescence-driven growth and capillary-driven motion on the way down. Bumps that are rationally designed to integrate these mechanisms are able to grow and transport large droplets even against gravity and overcome the effect of an unfavourable temperature gradient. We further observe an unprecedented sixfold-higher exponent of growth rate, faster onset, higher steady-state turnover rate, and a greater volume of water collected compared to other surfaces. We envision that this fundamental understanding and rational design strategy can be applied to a wide range of water-harvesting and phase-change heat-transfer applications.

Prognostic impact of collaterals in patients with a coronary chronic total occlusion: A meta-analysis of over 3,000 patients.

OBJECTIVES: To assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO. BACKGROUND: Coronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown. METHODS: A search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all-cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals. RESULTS: Twelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39-2.04) or lower rates of all-cause mortality (OR: 0.81, 95% CI: 0.42-1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10-14.85). CONCLUSION: The presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure.

Free Thiol ß2-GPI (ß-2-Glycoprotein-I) Provides a Link Between Inflammation and Oxidative Stress in Atherosclerotic Coronary Artery Disease.

OBJECTIVE: Atherosclerotic coronary artery disease is well recognised as an inflammatory disorder that is also influenced by oxidative stress. ß2-GPI (ß-2-glycoprotein-I) is a circulating plasma protein that undergoes post-translational modification and exists in free thiol as well as oxidized forms. The aim of this study was to assess the association between these 2 post-translational redox forms of ß2-GPI and atherosclerotic coronary artery disease. Approach and Results: Stable patients presenting for elective coronary angiography or CT coronary angiography were prospectively recruited. A separate group of patients after reperfused ST-segment-elevation myocardial infarction formed an acute coronary syndrome subgroup. All patients had collection of fasting serum and plasma for quantification of total and free thiol ß2-GPI. Coronary artery disease extent was quantified by the Syntax and Gensini scores. A total of 552 patients with stable disease and 44 with acute coronary syndrome were recruited. While total ß2-GPI was not associated with stable coronary artery disease, a higher free thiol ß2-GPI was associated with its presence and extent. This finding remained significant after correcting for confounding variables, and free thiol ß2-GPI was a better predictor of stable coronary artery disease than hs-CRP (high-sensitivity C-reactive protein). Paradoxically, there were lower levels of free thiol ß2-GPI after ST-segment-elevation myocardial infarction. CONCLUSIONS: Free thiol ß2-GPI is a predictor of coronary artery disease presence and extent in stable patients. Free thiol ß2-GPI was a better predictor than high-sensitivity C-reactive protein.

The indications and utility of adjunctive imaging modalities for chronic total occlusion (CTO) intervention.

Coronary chronic total occlusions (CTO) are common in patients undergoing coronary angiography, yet the optimal management strategy remains uncertain, with conflicting results from randomized trials. Appropriate patient selection and careful periprocedural planning are imperative for successful patient management. We review the role of adjunctive imaging modalities including myocardial perfusion imaging (MPI), cardiac magnetic resonance imaging (CMR), echocardiography and computed tomography coronary angiography (CTCA) in myocardial ischemic quantification, myocardial viability assessment, as well as procedural planning for CTO revascularization. An appreciation of the value, indications and limitations of these modalities prior to planned intervention are essential for optimal management.

Prognostic implications of the rapid recruitment of coronary collaterals during ST elevation myocardial infarction (STEMI): a meta-analysis of over 14,000 patients.

Acute coronary collateralisation of an infarct-related arterial (IRA) territory may be identified during angiography for ST elevation myocardial infarction (STEMI). Whether the presence or absence of these collaterals affects outcomes remains uncertain. A search of EMBASE, MEDLINE and Cochrane Library, using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines was conducted to identify studies which reported on the association between coronary collaterals and in-hospital and longer term mortality, left ventricular ejection fraction (LVEF), risk of repeat acute myocardial infarction (AMI) and repeat revascularisation. Patients with Rentrop grade 0 or 1 were defined as poor collaterals whilst those with Rentrop grade two or three were defined as those with robust collaterals. Studies were eligible if they included patients ≥ 18 years of age who had immediate coronary angiography for STEMI. Included studies were observational which recorded the degree of collateral blood flow to the IRA. Two investigators reviewed all citations using a predefined protocol with final consensus for all studies, the data from which was then independently entered to ensure fidelity of results. Inverse variance random effects model for the meta-analysis along with risk of bias assessment was performed. 20 studies with a total of 14,608 patients were identified and included in the analysis. Patients with robust collaterals had lower mortality (OR 0.55, 95% CI 0.48-0.64), both in-hospital (OR 0.47, 95% CI 0.35-0.63) and longer term (OR 0.58, 95% CI 0.46-0.75). Patients with robust collaterals also had a higher mean LVEF (SMD 0.23, 95% CI 0.10-0.37). There was no difference in the rates of AMI or repeat revascularisation between patients with robust or poor collaterals. The presence of robust collaterals during STEMI is associated with reduced in-hospital and longer term mortality and improved left ventricular function. These findings have implications for prognostication and identifying patients who require close monitoring following STEMI.

Both surgical and percutaneous revascularization improve prognosis in patients with a coronary chronic total occlusion (CTO) irrespective of collateral robustness.

The impact of surgical or percutaneous coronary revascularization on prognosis in patients with a chronic total occlusion (CTO) remains uncertain. Particularly, whether revascularization of those with robust coronary collaterals improves prognosis is unknown. The objective of this study was to determine the predictors and prognostic impact of revascularization of a CTO, and to determine the clinical impact of robust coronary collaterals. Patients with a CTO diagnosed on coronary angiography between Jul 2010 and Dec 2019 were included in this study. Management strategy of the CTO was defined as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical management. The degree of collateral robustness was determined by the Rentrop grading classification. Demographic, angiographic and clinical outcomes were recorded. A total of 954 patients were included in the study, of which 186 (19.5%) patients underwent CTO PCI, 296 (31.0%) patients underwent CABG and 472 (49.5%) patients underwent medical management of the CTO. 166 patients (17.4%) had Rentrop grade zero or one collaterals, 577 (60.5%) patients had Rentrop grade two and 211 (22.1%) had Rentrop grade three collaterals. The independent predictors of medical management of the CTO were older age, greater stenosis in the donor vessel, an emergent indication for angiography, a non-LAD CTO and female sex. The degree of collateral robustness was not associated with long-term mortality, while patients who were revascularized either through CABG or PCI had a significantly lower mortality compared to medical management alone (p < 0.0001). In patients with a CTO, the presence of robust collaterals is not associated with prognosis, while both surgical and percutaneous revascularization is associated with improved prognosis. Further research into the optimal revascularization strategy for a CTO is required.

Influence of Obstructive Sleep Apnoea Severity on Coronary Collateral Recruitment During Coronary Occlusion.

PURPOSE: Obstructive sleep apnoea (OSA) which results in hypoxia may affect the ability to recruit coronary collaterals. The aim of this study was to determine whether the severity of OSA affects collateral recruitment in patients with total coronary occlusions. METHODS: Patients with total coronary artery occlusion were reviewed. Records from the sleep investigation laboratory were reviewed to identify those patients who had undergone diagnostic polysomnography. Robust coronary collaterals were those with Rentrop grade 2 or 3 collaterals. RESULTS: Sixty-four patients with a total coronary occlusion had polysomnography performed, of whom 60 patients had OSA. Thirty-two patients (53.3%) had poor collaterals, whilst 28 (46.7%) had robust collaterals. Twenty-four (40%) patients had mild OSA, 10 (16.7%) had moderate OSA and 26 (43.3%) had severe OSA. Patients with robust collaterals were more likely to be males (96.4% vs 74.3%, p < 0.05) and have a history of hypercholesterolaemia (88.9% vs 51.6%, p < 0.01). Patients with robust collaterals had a lower apnoea-hypopnoea index (13.6 vs 45.5, p < 0.05), a higher MinSaO2 (85.4% vs 79.8%, p < 0.05), less time SaO2 < 90% (0 min vs 30.4 min, p < 0.05) and lower oxygen desaturation index (6.9 vs 26.8, p < 0.05). Those with moderate OSA had a higher mean Rentrop grade (1.6 ± 0.3) than those with mild OSA (1.5 ± 1.1) and severe OSA (0.6 ± 0.2). CONCLUSION: The presence of more severe OSA is associated with poorer coronary collateral recruitment in patients with total coronary artery occlusion. The effect of treatment of OSA on subsequent ability to recruit collaterals and other cardioprotective mechanisms requires further research.

Influence of Obstructive Sleep Apnoea on Outcomes in Patients With ST Elevation Myocardial Infarction (STEMI): the Role of the Coronary Collateral Circulation.

BACKGROUND: Obstructive sleep apnoea (OSA) occurs frequently in patients with coronary artery disease, with associated intermittent hypoxia a possible stimulus for coronary collateral recruitment through ischaemic preconditioning. We sought to determine whether OSA affects recruitment of coronary collaterals and prognosis of patients presenting with ST elevation myocardial infarction (STEMI). METHODS: Patients with a STEMI undergoing percutaneous coronary intervention (PCI) from July 2010 to December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA. Patients with robust collaterals were defined as Rentrop Grade 2 or 3. RESULTS: 1,863 patients were included, of which 143 (7.7%) patients had documented evidence of OSA in their health record. Patients with OSA had a higher body mass index (BMI) (30.2 kg/m2 vs 27 kg/m2, p<0.0001), greater rate of hypertension (61.1% vs 45.1%, p<0.0001), hypercholesterolaemia (47.4% vs 38.4%, p<0.05) and diabetes mellitus (22.6% vs 15.9%, p<0.05). Patients with OSA were more likely to have robust coronary collaterals (OR: 2.2 [95% CI: 1.5-3.2]) and a lower rate of left ventricular (LV) impairment (50.7% vs 63.1%, p<0.01), a higher LV ejection fraction (50.3% vs 46.7%, p<0.0001) and a lower peak troponin-I level (26,452 ng/L vs 39,469 ng/L, p<0.01). There were no differences in rates of in-hospital or longer term mortality, in patients with OSA compared to those without. CONCLUSIONS: Patients with documented OSA presenting with STEMI appear to have more robust coronary collaterals observed on angiography which likely mediates lower myocardial necrosis. Broader implications of this finding on treatment require further investigation.

The structural origins of brittle star arm kinematics: An integrated tomographic, additive manufacturing, and parametric modeling-based approach.

Brittle stars are known for the high flexibility of their arms, a characteristic required for locomotion, food grasping, and for holding onto a great diversity of substrates. Their high agility is facilitated by the numerous discrete skeletal elements (ossicles) running through the center of each arm and embedded in the skin. While much has been learned regarding the structural diversity of these ossicles, which are important characters for taxonomic purposes, their impact on the arms' range of motion, by contrast, is poorly understood. In the present study, we set out to investigate how ossicle morphology and skeletal organization affect the flexibility of brittle star arms. Here, we present the results of an in-depth analysis of three brittle star species (Ophioplocus esmarki, Ophiopteris papillosa, and Ophiothrix spiculata), chosen for their different ranges of motion, as well as spine size and orientation. Using an integrated approach that combines behavioral studies with parametric modeling, additive manufacturing, micro-computed tomography, scanning electron microscopy, and finite element simulations, we present a high-throughput workflow that provides a fundamental understanding of 3D structure-kinematic relationships in brittle star skeletal systems.

Spontaneous coronary collateral recruitment in patients with recurrent ST elevation myocardial infarction (STEMI).

The spontaneous recruitment of acute coronary collaterals in the setting of an ST elevation myocardial infarction (STEMI) is seen frequently in those patients undergoing primary percutaneous coronary intervention (pPCI) and is associated with improved clinical outcomes. However, it is unknown whether in patients who present with a recurrent STEMI, the degree of collateral recruitment remains the same as in the index procedure. We reviewed all patients presenting to our tertiary centre with a STEMI undergoing primary or rescue percutaneous coronary intervention (PCI) from July 2010 until December 2018. We identified patients who presented with a recurrent STEMI following their index procedure. We defined patients with poor collateral recruitment as Rentrop grade 0 or 1, whilst patients with robust collateral recruitment as Rentrop grade 2 or 3. Of the 1795 patients who were identified, there were 27 cases in 25 patients who presented with a repeat STEMI following their index procedure. The median time between cases was 12.8 days (IQR 2.3-589.5 days). Compared to the index case, there was no statistically significant difference in the degree of collateral recruitment in recurrent presentations (Z = - 0.378, p = 0.70). In those patients presenting more than 6 months following the index procedure, the median time between cases was 654.5 days (IQR 479.5-1151.9). There was no difference in the degree of collateral recruitment in recurrent presentations (Z = 0.000, p = 1.0). Cases which had poorer collateral recruitment in recurrent presentations were less likely to be current smokers (0% vs 50%, p < 0.001) and less likely to have diabetes (0% vs 27.3%, p < 0.05) The recruitment of spontaneous coronary collaterals remains constant in recurrent STEMI presentations suggesting an innate biological process rather than merely a manifestation of alteration of haemodynamic blood flow. Further investigations to identify these processes is required.

Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro.

Here we describe the development of a human lung 'small airway-on-a-chip' containing a differentiated, mucociliary bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which allows for analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to interleukin-13 (IL-13) reconstituted the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined with epithelial cells from individuals with chronic obstructive pulmonary disease recapitulated features of the disease such as selective cytokine hypersecretion, increased neutrophil recruitment and clinical exacerbation by exposure to viral and bacterial infections. With this robust in vitro method for modeling human lung inflammatory disorders, it is possible to detect synergistic effects of lung endothelium and epithelium on cytokine secretion, identify new biomarkers of disease exacerbation and measure responses to anti-inflammatory compounds that inhibit cytokine-induced recruitment of circulating neutrophils under flow.

A facile approach to enhance antigen response for personalized cancer vaccination.

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR-PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR-PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.