BloodSurf 2017: News from the blood-biomaterial frontier.

From stents and large-diameter vascular grafts, to mechanical heart valves and blood pumps, blood-contacting devices are enjoying significant clinical success owing to the application of systemic antiplatelet and anticoagulation therapies. On the contrary, research into material and device hemocompatibility aimed at alleviating the need for systemic therapies has suffered a decline. This research area is undergoing a renaissance fueled by recent fundamental insights into coagulation and inflammation that are offering new avenues of investigation, the growing recognition of the limitations facing existing therapeutic approaches, and the severity of the cardiovascular disorders epidemic. This Opinion article discusses clinical needs for hemocompatible materials and the emerging research directions for fulfilling those needs. Based on the 2017 BloodSurf conference that brought together clinicians, scientists, and engineers from academia, industry, and regulatory bodies, its purpose is to draw the attention of the wider clinical and scientific community to stimulate further growth. STATEMENT OF SIGNIFICANCE: The article highlights recent fundamental insights into coagulation, inflammation, and blood-biomaterial interactions that are fueling a renaissance in the field of material hemocompatibility. It will be useful for clinicians, scientists, engineers, representatives of industry and regulatory bodies working on the problem of developing hemocompatible materials and devices for treating cardiovascular disorders.

Tunability of liquid-infused silicone materials for biointerfaces.

The ability to control the properties of bio-inspired liquid-infused surfaces is of interest in a wide range of applications. Liquid layers created using oil-infused polydimethylsiloxane elastomers offer a potentially simple way of accomplishing this goal through the adjustment of parameters such as curing agent ratio and oil viscosity. In this work, the effect of tuning these compositional parameters on the properties of the infused polymer are investigated, including infusion dynamics, stiffness, longevity in the face of continuous liquid overlayer removal, and resistance to bacterial adhesion. It is found that that curing agent concentration appears to have the greatest impact on the functionality of the system, with a lower base-to-curing agent ratio resulting in both increased longevity and improved resistance to adhesion by Escherichia coli. A demonstration of how these findings may be implemented to introduce patterned wettability to the surface of the infused polymers is presented by controlling the spatial arrangement of bacteria. These results demonstrate a new degree of control over immobilized liquid layers and will facilitate their use in future applications.

Bacterial Interactions with Immobilized Liquid Layers.

Bacterial interactions with surfaces are at the heart of many infection-related problems in healthcare. In this work, the interactions of clinically relevant bacteria with immobilized liquid (IL) layers on oil-infused polymers are investigated. Although oil-infused polymers reduce bacterial adhesion in all cases, complex interactions of the bacteria and liquid layer under orbital flow conditions are uncovered. The number of adherent Escherichia coli cells over multiple removal cycles increases in flow compared to static growth conditions, likely due to a disruption of the liquid layer continuity. Surprisingly, however, biofilm formation appears to remain low regardless of growth conditions. No incorporation of the bacteria into the layer is observed. Bacterial type is also found to affect the number of adherent cells, with more E. coli remaining attached under dynamic orbital flow than Staphylococcus aureus, Pseudomonas aeruginosa under identical conditions. Tests with mutant E. coli lacking flagella confirm that flagella play an important role in adhesion to these surfaces. The results presented here shed new light on the interaction of bacteria with IL layers, highlighting the fundamental differences between oil-infused and traditional solid interfaces, as well as providing important information for their eventual translation into materials that reduce bacterial adhesion in medical applications.

An immobilized liquid interface prevents device associated bacterial infection in vivo.

Virtually all biomaterials are susceptible to biofilm formation and, as a consequence, device-associated infection. The concept of an immobilized liquid surface, termed slippery liquid-infused porous surfaces (SLIPS), represents a new framework for creating a stable, dynamic, omniphobic surface that displays ultralow adhesion and limits bacterial biofilm formation. A widely used biomaterial in clinical care, expanded polytetrafluoroethylene (ePTFE), infused with various perfluorocarbon liquids generated SLIPS surfaces that exhibited a 99% reduction in S. aureus adhesion with preservation of macrophage viability, phagocytosis, and bactericidal function. Notably, SLIPS modification of ePTFE prevents device infection after S. aureus challenge in vivo, while eliciting a significantly attenuated innate immune response. SLIPS-modified implants also decrease macrophage inflammatory cytokine expression in vitro, which likely contributed to the presence of a thinner fibrous capsule in the absence of bacterial challenge. SLIPS is an easily implementable technology that provides a promising approach to substantially reduce the risk of device infection and associated patient morbidity, as well as health care costs.

Infused polymers for cell sheet release.

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

Immobilized liquid layers: A new approach to anti-adhesion surfaces for medical applications.

Surface fouling and undesired adhesion are nearly ubiquitous problems in the medical field, complicating everything from surgeries to routine daily care of patients. Recently, the concept of immobilized liquid (IL) interfaces has been gaining attention as a highly versatile new approach to antifouling, with a wide variety of promising applications in medicine. Here, we review the general concepts behind IL layers and discuss the fabrication strategies on medically relevant materials developed so far. We also summarize the most important findings to date on applications of potential interest to the medical community, including the use of these surfaces as anti-thrombogenic and anti-bacterial materials, anti-adhesive textiles, high-performance coatings for optics, and as unique platforms for diagnostics. Although the full potential and pitfalls of IL layers in medicine are just beginning to be explored, we believe that this approach to anti-adhesive surfaces will prove broadly useful for medical applications in the future.