________________________________________________________________Countless lives have been saved by implantable medical devices (e.g., total artificial hearts, ventricular assist devices, pacemakers, cardioverterdefibrillators, and central lines) and extracorporeal devices that flow whole human blood outside the body through indwelling catheters and external circuits, during cardiopulmonary bypass (CPB), hemodialysis, and extracorporeal membrane oxygenation (ECMO) 1,2 . However, the need to co-administer soluble anticoagulant drugs, such as heparin, with many of these procedures, significantly reduces their safety and hampers their effectiveness 3,4 . Without systemic anticoagulation, these extracorporeal and indwelling devices can rapidly occlude due to thrombosis because clots form when fibrin and platelets in the flowing blood adhere to the surfaces of these artificial materials 5 . Unfortunately, heparin causes significant morbidity and mortality including post-operative bleeding, thrombocytopenia, hypertriglyceridemia, hyperkalemia and hypersensitivity 6 , and its use is contraindicated in several patient populations 7 . In fact, the majority of drug-related deaths from adverse clinical events in the UnitedStates are due to systemic anticoagulation 8 .This need to prevent blood clotting while minimizing administration of anticoagulant drugs has led to the search for biomaterial surface coatings that can directly suppress blood clot formation. The most successful approach to date has been to chemically immobilize heparin on blood-contacting surfaces to reduce thrombosis and lower anticoagulant administration 9,10 . Although this approach has been widely adopted, major limitations persist because the surface-bound heparin leaches, resulting in a progressive loss of anticoagulation 24,25 . Importantly, the TP continues to retain the free LP as a thin mobile liquid layer even when the surface is challenged with a flowing immiscible fluid, such as blood (Fig. 1a). We refer to this unique anti-thrombogenic bilayer composed of the TP and LP coating as a Tethered-Liquid Perfluorocarbon (TLP) surface. RESULTS A generic blood repellent surface coatingTo test the anti-adhesive properties of the TLP coating method, we examined surface adhesion of fresh whole human blood on an acrylic surface sloped at an angle of 30 degrees, with or without a TLP coating composed of tethered perfluorohexane and liquid perfluorodecalin. Blood droplets immediately adhered to the control uncoated acrylic surface and left a trail of blood components over the course of 5 sec (Fig. 1b, top, Supplementary Fig. 1 and Supplementary Movie 1).In contrast, when the same surface was coated with TLP, the blood droplet almost immediately slid off the surface (< 0.3 sec), and remarkably, there was no evidence of any residual blood trail (Fig. 1b, Supplementary Fig. 1 and Supplementary Movie 2). We quantified blood adhesion to surfaces by measuring the minimum angle required to cause a droplet to slide ("sliding angle") ( Fig. 1c). Control uncoated s...

Material stability and dissolution in aqueous media are key issues to address in the development of a new nanomaterial intended for technological application. Dissolution phenomena affect biological and environmental persistence; fate, transport, and biokinetics; device and product stability; and toxicity pathways and mechanisms. This article shows that MoS2 nanosheets are thermodynamically and kinetically unstable to O2-oxidation under ambient conditions in a vareity of aqueous media. The oxidation is accompanied by nanosheet degradation and release of soluble molybdenum and sulfur species, and generates protons that can colloidally destabilize the remaining sheets. The oxidation kinetics are pH-dependent, and a kinetic law is developed for use in biokinetic and environmental fate modelling. MoS2 nanosheets fabricated by chemical exfoliation with n-butyl-lithium are a mixture of 1T (primary) and 2H (secondary) phases and oxidize rapidly with a typical half-life of 1–30 days. Ultrasonically exfoliated sheets are in pure 2H phase, and oxidize much more slowly. Cytotoxicity experiments on MoS2 nanosheets and molybdate ion controls reveal the relative roles of the nanosheet and soluble fractions in the biological response. These results indicate that MoS2 nanosheets will not show long-term persistence in living systems and oxic natural waters, with important implications for biomedical applications and environmental risk.

The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.electrophysiology | connectivity | silk | scaffold | traumatic brain injury

Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.

Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent “cold chain” to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self-standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 °C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world.

Multigenerational graphene oxide architectures can be programmed by specific sequences of mechanical deformations. Each new deformation results in a progressively larger set of features decorated by smaller preexisting patterns, indicating a structural "memory." It is shown that these multiscale architectures are superhydrophobic and display excellent functionality as electrochemical electrodes.

IntroductionVitamin D plays a key role in immune function. Deficiency may aggravate the incidence and outcome of infectious complications in critically ill patients. We aimed to evaluate the prevalence of vitamin D deficiency and the correlation between serum 25-hydroxyvitamin D (25(OH) D) and hospital mortality, sepsis mortality and blood culture positivity.MethodsIn a single-center retrospective observational study at a tertiary care center in Graz, Austria, 655 surgical and nonsurgical critically ill patients with available 25(OH) D levels hospitalized between September 2008 and May 2010 were included. Cox regression analysis adjusted for age, gender, severity of illness, renal function and inflammatory status was performed. Vitamin D levels were categorized by month-specific tertiles (high, intermediate, low) to reflect seasonal variation of serum 25(OH) D levels.ResultsOverall, the majority of patients were vitamin D deficient (<20 ng/ml; 60.2%) or insufficient (≥20 and <30 ng/dl; 26.3%), with normal 25(OH) D levels (>30 ng/ml) present in only 13.6%. The prevalence of vitamin D deficiency and mean 25(OH) D levels was significantly different in winter compared to summer months (P <0.001). Hospital mortality was 20.6% (135 of 655 patients). Adjusted hospital mortality was significantly higher in patients in the low (hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.31 to 3.22) and intermediate (HR 1.92, 95% CI 1.21 to 3.06) compared to the high tertile. Sepsis was identified as cause of death in 20 of 135 deceased patients (14.8%). There was no significant association between 25(OH) D and C-reactive protein (CRP), leukocyte count or procalcitonin levels. In a subgroup analysis (n = 244), blood culture positivity rates did not differ between tertiles (23.1% versus 28.2% versus 17.1%, P = 0.361).ConclusionsLow 25(OH) D status is significantly associated with mortality in the critically ill. Intervention studies are needed to investigate the effect of vitamin D substitution on mortality and sepsis rates in this population.

Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing and diverse material formats. We report on functional release of antibiotics spanning a range of chemical properties from different material formats of silk (films, microspheres, hydrogels, coatings). The release of penicillin and ampicillin from bulk-loaded silk films, drug-loaded silk microspheres suspended in silk hydrogels and bulk-loaded silk hydrogels was investigated and in vivo efficacy of ampicillin-releasing silk hydrogels was demonstrated in a murine infected wound model. Silk sponges with nanofilm coatings were loaded with gentamicin and cefazolin and release was sustained for 5 and 3 days, respectively. The capability of silk antibiotic carriers to sequester, stabilize and then release bioactive antibiotics represents a major advantage over implants and pumps based on liquid drug reservoirs where instability at room or body temperature is limiting. The present studies demonstrate that silk biomaterials represent a novel, customizable antibiotic platform for focal delivery of antibiotics using a range of material formats (injectable to implantable).