________________________________________________________________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...

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.

We review the rational choice, the analysis, the depletion and the properties imparted by the liquid layer in liquid-infused surfaces – a new class of low-adhesion surface.

Elastin is a versatile elastic protein that dominates flexible tissues capable of recoil, and facilitates commensurate cell interactions in these tissues in all higher vertebrates. Elastin's persistence and insolubility hampered early efforts to construct versatile biomaterials. Subsequently the field has progressed substantially through the adapted use of solubilized elastin, elastin-based peptides and the increasing availability of recombinant forms of the natural soluble elastin precursor, tropoelastin. These interactions allow for the formation of a sophisticated range of biomaterial constructs and composites that benefit from elastin's physical properties of innate assembly and elasticity, and cell interactive properties as discussed in this tutorial review.

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Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines.

Metastases in breast cancer are a vital concern in treatment, with epidermal growth factor receptor and ErbB2 strongly implicated in mediating tumor invasion and spreading. In this study, we investigated the role of decorin in suppressing both primary breast carcinomas and pulmonary metastases. We show that decorin causes marked growth suppression both in vitro and in vivo using a metastatic breast cancer cell line and an orthotopic mammary carcinoma model. Treatment with decorin protein core reduced primary tumor growth by 70% and eliminated observed metastases. An adenoviral vector containing the decorin transgene caused primary tumor retardation of 70%, in addition to greatly reducing observed metastases. Moreover, we demonstrate that ErbB2 phosphorylation and total receptor protein levels are reduced in this model system upon de novo expression of decorin under the control of a doxycycline-inducible promoter. Primary tumor growth in vivo was reduced by up to 67% upon decorin induction, and pulmonary metastases were markedly hampered as well. These effects are likely occurring through decorin's long-term downregulation of the ErbB2 tyrosine kinase cascade. These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapeutics for metastatic breast cancer.

The stability and longevity of surface-stabilized lubricant layers is a critical question in their application as low-and non-fouling slippery surface treatments in both industry and medicine. Here, we investigate lubricant loss from surfaces under flow in water using both quantitative analysis and visualization, testing the effects of underlying surface type (nanostructured versus flat), as well as flow rate in the physiologically-relevant range, lubricant type, and time. We find lubricant losses on the order of only ng/cm 2 in a closed system, indicating that these interfaces are relatively stable under the flow conditions tested. No notable differences emerged between surface type, flow rate, lubricant type, or time. However, exposure of the lubricant layers to an air/water interface did significantly increase the amount of lubricant removed from the surface, leading to disruption of the layer. These results may help in the development and design of materials using surface-immobilized lubricant interfaces for repellency under flow conditions.