Bionanointerfaces

Cells of all types take cues from the surfaces they encounter in their environment. The cells extract any or all of the mechanical, chemical, spatial, and even temporal information from the surface, but which features they read and how they integrate and translate them into specific behavioral responses is still almost a black box. 

Projects

Vascularized self-lubricating surfaces

Fig. 1: Bio-inspired vascularized fouling-release surfaces.
Fig. 2: Bio-inspired vacularized fouling-release surfaces.
Fig. 3: (A) Schematic of the process to make either infused PDMS or vascularized, infused PDMS. For simple infused PDMS (upper row), cured PDMS is placed in a bath of silicone oil which diffuses into the PDMS solid. For vascularized PDMS, the vascular pattern is created before curing. The sample is then infused externally with silicone oil in the same manner as the non-vascularized PDMS, or internally through filling the vascular network, or both. (B) Methods of creating vascular networks within PDMS: 1) An encased network is created using a 3D mold (a) to create the pattern in PDMS (b). The mold is removed from the cured PMDS (c) and the pattern is covered with a second sheet of PDMS (d and e) which is chemically bonded to the pattern using plasma. (i) an image of a 3D leaf vasculature network after encasing. 2) An embedded network is created following the procedures developed by Lewis et al. (citation). (a) A pattern of 20% w/w pluronic F127 gel at 25 °C is embedded in uncured PDMS. (b) The PDMS is allowed to cure, cooled to 4 °C, and the liquid pluronic is evacuated. (c) The channel is refilled with silicone oil. (i) An image of fluorescently dyed PDMS in a hand-drawn sinuous channel, (ii) a hand-drawn leaf-shape network, and (iii) a 3D-printed linear network.
Fig. 6: (A) Surface coverage of biofilm remaining on lubricant-infused PDMS versus glass control surfaces after incubation in and removal from the liquid medium containing C. reinhardtii, D. salina, or N. oculata. For all three species, there was a significant reduction in the amount of biofilm remaining on the SLIPS surfaces (P < 0.05). (B) Images of the substrates used in the analysis.

We have recently developed a technique for fabricating nanostructured surfaces that enables us to choose and independently vary any combination of geometry, spacing, stiffness, and chemistry, and are using it to analyze how surface features direct bacterial assembly, mammalian cell development, and marine invertebrate settlement at a level of systematic detail that was previously not possible.

As our insight into the cell-nanosurface interface develops, the same fabrication technique will enable us to design and construct surfaces that encode instructions for cell behavior for purposes ranging from anti-biofilm coatings to neural chips to organ development scaffolds.

Alvarez MM, Aizenberg J, Analoui M, Andrews AM, Bisker G, Boyden ES, Kamm RD, Karp JM, Mooney DJ, Oklu R, et al. Emerging Trends in Micro- and Nanoscale Technologies in Medicine: From Basic Discoveries to Translation. ACS Nano. 2017;11 (6) :5195-5214.Abstract

We discuss the state of the art and innovative micro- and nanoscale technologies that are finding niches and opening up new opportunities in medicine, particularly in diagnostic and therapeutic applications. We take the design of point-of-care applications and the capture of circulating tumor cells as illustrative examples of the integration of micro- and nanotechnologies into solutions of diagnostic challenges. We describe several novel nanotechnologies that enable imaging cellular structures and molecular events. In therapeutics, we describe the utilization of micro- and nanotechnologies in applications including drug delivery, tissue engineering, and pharmaceutical development/testing. In addition, we discuss relevant challenges that micro- and nanotechnologies face in achieving cost-effective and widespread clinical implementation as well as forecasted applications of micro- and nanotechnologies in medicine.

Sutton A, Shirman T, Timonen JVI, England GT, Kim P, Kolle M, Ferrante T, Zarzar LD, Strong E, Aizenberg J. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation. Nat. Commun. 2017;8 :14700.Abstract

Mechanical forces in the cell’s natural environment have a crucial impact on growth,
differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging from the entire surface to the subcellular, and response times on the order of seconds. These capabilities are not matched by any other method, and this versatile material has the potential to bridge the performance gap between the existing single cell micro-manipulation and 2D cell sheet mechanical stimulation techniques.

Sunny S, Cheng G, Daniel D, Lo P, Ochoa S, Howell C, Vogel N, Majid A, Aizenberg J. Transparent antifouling material for improved operative field visibility in endoscopy. Proc. Nat. Acad. Sci. 2016;113 (42) :11676-11681.Abstract

Inspection devices are frequently occluded by highly contaminating fluids that disrupt the visual field and their effective operation. These issues are particularly striking in endoscopes, where the diagnosis and treatment of diseases are compromised by the obscuring of the operative field by body fluids. Here we demonstrate that the application of a liquid-infused surface coating strongly repels sticky biological secretions and enables an uninterrupted field of view. Extensive bronchoscopy procedures performed in vivo on a porcine model shows significantly reduced fouling, resulting in either unnecessary or ∼10–15 times shorter and less intensive lens clearing procedures compared with an untreated endoscope.

Camera-guided instruments, such as endoscopes, have become an essential component of contemporary medicine. The 15–20 million endoscopies performed every year in the United States alone demonstrate the tremendous impact of this technology. However, doctors heavily rely on the visual feedback provided by the endoscope camera, which is routinely compromised when body fluids and fogging occlude the lens, requiring lengthy cleaning procedures that include irrigation, tissue rubbing, suction, and even temporary removal of the endoscope for external cleaning. Bronchoscopies are especially affected because they are performed on delicate tissue, in high-humidity environments with exposure to extremely adhesive biological fluids such as mucus and blood. Here, we present a repellent, liquid-infused coating on an endoscope lens capable of preventing vision loss after repeated submersions in blood and mucus. The material properties of the coating, including conformability, mechanical adhesion, transparency, oil type, and biocompatibility, were optimized in comprehensive in vitro and ex vivo studies. Extensive bronchoscopy procedures performed in vivo on porcine lungs showed significantly reduced fouling, resulting in either unnecessary or ∼10–15 times shorter and less intensive lens clearing procedures compared with an untreated endoscope. We believe that the material developed in this study opens up opportunities in the design of next-generation endoscopes that will improve visual field, display unprecedented antibacterial and antifouling properties, reduce the duration of the procedure, and enable visualization of currently unreachable parts of the body, thus offering enormous potential for disease diagnosis and treatment.

MacCallum N, Howell C, Kim P, Sun D, Friedlander R, Ranisau J, Ahanotu O, Lin JJ, Vena A, Hatton B, et al. Liquid-Infused Silicone As a Biofouling-Free Medical Material. ACS Biomater. Sci. Eng. 2015;1 (1) :43-51.Abstract
There is a dire need for infection prevention strategies that do not require the use of antibiotics, which exacerbate the rise of multi- and pan-drug resistant infectious organisms. An important target in this area is the bacterial attachment and subsequent biofilm formation on medical devices (e.g., catheters). Here we describe nonfouling, lubricant-infused slippery polymers as proof-of-concept medical materials that are based on oil-infused polydimethylsiloxane (iPDMS). Planar and tubular geometry silicone substrates can be infused with nontoxic silicone oil to create a stable, extremely slippery interface that exhibits exceptionally low bacterial adhesion and prevents biofilm formation. Analysis of a flow culture of Pseudomonas aeruginosa through untreated PDMS and iPDMS tubing shows at least an order of magnitude reduction of biofilm formation on iPDMS, and almost complete absence of biofilm on iPDMS after a gentle water rinse. The iPDMS materials can be applied as a coating on other polymers or prepared by simply immersing silicone tubing in silicone oil, and are compatible with traditional sterilization methods. As a demonstration, we show the preparation of silicone-coated polyurethane catheters and significant reduction of Escherichia coli and Staphylococcus epidermidis biofilm formation on the catheter surface. This work represents an important first step toward a simple and effective means of preventing bacterial adhesion on a wide range of materials used for medical devices.
Yao X, Dunn S, Kim P, Duffy M, Alvarenga J, Aizenberg J. Fluorogel Elastomers with Tunable Transparency, Elasticity, Shape- Memory, and Antifouling Properties. Angew. Chem. Int. Ed. 2014;53 (17) :4418-4422.Abstract

Omniphobic fluorogel elastomers were prepared by photocuring perfluorinated acrylates and a perfluoropolyether crosslinker. By tuning either the chemical composition or the temperature that control the crystallinity of the resulting polymer chains, a broad range of optical and mechanical properties of the fluorogel can be achieved. After infusing with fluorinated lubricants, the fluorogels showed excellent resist- ance to wetting by various liquids and anti-biofouling behavior, while maintaining cytocompatiblity.

Hashmi B, Zarzar LD, Mammoto T, Jiang A, Aizenberg J, Ingber DE. Developmentally-Inspired Shrink-Wrap Polymers for Mechanical Induction of Tissue Differentiation. Adv. Mater. 2014;26 (20) :3253-3257.Abstract
A biologically inspired thermoresponsive polymer has been developed that mechanically induces tooth differentiation in vitro and in vivo by promoting mesenchymal cell compaction as seen in each pore of the scaffold. This normally occurs during the physiological mesenchymal condensation response that triggers tooth formation in the embryo.

Clinging to crevices, E. coli thrive, Harvard press release, April 10, 2013.