Publications

2017
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.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.

2017_alvarez_et_al_acsnano.pdf
Hou X, Zhang YS, Trujillo-de Santiago MMA, Ribas J, Jonas SJ, Weiss PS, Andrews AM, Aizenberg J, Khademhosseini A. Interplay between materials and microfluidics. Nature Reviews Materials. 2017;2 :17016.Abstract

Developments in the field of microfluidics have triggered technological revolutions in many disciplines, including chemical synthesis, electronics, diagnostics, single-cell analysis, micro- and nanofabrication, and pharmaceutics. In many of these areas, rapid growth is driven by the increasing synergy between fundamental materials development and new microfluidic capabilities. In this Review, we critically evaluate both how recent advances in materials fabrication have expanded the frontiers of microfluidic platforms and how the improved microfluidic capabilities are, in turn, furthering materials design. We discuss how various inorganic and organic materials enable the fabrication of systems with advanced mechanical, optical, chemical, electrical and biointerfacial properties — in particular, when these materials are combined into new hybrids and modular configurations. The increasing sophistication of microfluidic techniques has also expanded the range of resources available for the fabrication of new materials, including particles and fibres with specific functionalities, 3D (bio)printed composites and organoids. Together, these advances lead to complex, multifunctional systems, which have many interesting potential applications, especially in the biomedical and bioengineering domains. Future exploration of the interactions between materials science and microfluidics will continue to enrich the diversity of applications across engineering as well as the physical and biomedical sciences.

natrevmats201716.pdf
Kaplan CN, Noorduin WL, Li L, Sadza R, Folkertsma L, Aizenberg J, Mahadevan L. Controlled growth and form of precipitating microstructures. Science. 2017;355 :1395-1399.Abstract

Controlled self-assembly of three-dimensional shapes holds great potential for fabrication of functional materials. Their practical realization requires a theoretical framework to quantify and guide the dynamic sculpting of the curved structures that often arise in accretive mineralization. Motivated by a variety of bioinspired coprecipitation patterns of carbonate and silica, we develop a geometrical theory for the kinetics of the growth front that leaves behind thin-walled complex structures. Our theory explains the range of previously observed experimental patterns and, in addition, predicts unexplored assembly pathways. This allows us to design a number of functional base shapes of optical microstructures, which we synthesize to demonstrate their light-guiding capabilities. Overall, our framework provides a way to understand and control the growth and form of functional precipitating microsculptures.

science2017.kaplan_etal.pdf
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. Comm. 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.

2017_sutton_natcomm.pdf
Hu Y, Kim P, Aizenberg J. Harnessing structural instability and material instability in the hydrogel-actuated integrated responsive structures (HAIRS). Extreme Mechanics Letters. 2017;13 :84-90.Abstract

We describe the behavior of a temperature-responsive hydrogel actuated integrated responsive structure (HAIRS). The structure is constructed by embedding a rigid high-aspect-ratio post in a layer of poly(Nisopropylacrylamide) (PNIPAM) hydrogel which is bonded to a rigid substrate. As the hydrogel contracts, the post abruptly tilts. The HAIRS has demonstrated its broad applications in generating reversible micropattern formation, active optics, tunable wettability, and artificial homeostasis. To quantitatively describe and predict the system behavior, we construct an analytical model combining the structural instability, i.e. buckling of the post, and the material instability, i.e. the volume phase transition of PNIPAM hydrogel. The two instabilities of the system result in a large hysteresis in response to heating and cooling processes. Experimental results validate the predicted phenomenon of the abrupt tilting as temperature and large hysteresis in a heating-and-cooling cycle in the PNIPAM actuated HAIRS. Based on this model, we further discuss the influence of the material properties on the actuation of the structure.

hu_etal_eml.pdf
Kovalenko Y, Sotiri I, Timonen JVI, Overton JC, Homes G, Aizenberg J, Howell C. Bacterial Interactions with Immobilized Liquid Layer. Adv. Healthcare Mater. . 2017 :1600948.Abstract

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.

2017_kovalenko_ahm.pdf
Chen J, Howell C, Haller CA, Patel MS, Ayala P, Moravec KA, Dai E, Liu L, Sotiri I, Aizenberg M, et al. An immobilized liquid interface prevents device associated bacterial infection in vivo. Biomaterials [Internet]. 2017;113 :80-92. Publisher's VersionAbstract

 

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.

 

 

 

biomaterials_2016.an_immobilized_liquid_interface_prevents_device_associated_bacterial_infection.pdf
2016
Pouya C, Overvelde JTB, Kolle M, Aizenberg J, Bertoldi K, Weaver JC, Vukusic P. Characterization of a Mechanically Tunable Gyroid Photonic Crystal Inspired by the Butterfly Parides Sesostris. Adv. Optical Mater. . 2016;4 :99-105. 2016_pouya_etal_aom.pdf
Liu Y, Bhattacharya A, Kuksenok O, He X, Aizenberg M, Aizenberg J, Balazs AC. Computational modeling of oscillating fins that “catch and release“ targeted nanoparticles in bilayer flows. Soft Matter. 2016;12 :1374-1384.Abstract

A number of physiological processes in living organisms involve the selective ‘‘catch and release’’ of biomolecules. Inspired by these biological processes, we use computational modeling to design synthetic systems that can controllably catch, transport, and release specific molecules within the surrounding solution, and, thus, could be harnessed for effective separation processes within microfluidic devices. Our system consists of an array of oscillating, microscopic fins that are anchored onto the floor of a microchannel and immersed in a flowing bilayer fluid. The oscillations drive the fins to repeatedly extend into the upper fluid and then tilt into the lower stream. The fins exhibit a specified wetting interaction with the fluids and specific adhesive interactions with nanoparticles in the solution. With this setup, we determine conditions where the oscillating fins can selectively bind, and thus, ‘‘catch’’ target nanoparticles within the upper fluid stream and
then release these particles into the lower stream. We isolate the effects of varying the wetting interaction and the fins’ oscillation modes on the effective extraction of target species from the upper stream. Our findings provide fundamental insights into the system’s complex dynamics and yield guidelines for fabricating devices for the detection and separation of target molecules from complex fluids.

2016_liu_etal_softmatter.pdf
Jeon I, Cui J, Illeperuma WRK, Aizenberg J, Vlassak JJ. Extremely Stretchable and Fast Self-Healing Hydrogels. Adv. Mater. 2016;28 :4678-4683. 2016_jeon_etal_am.pdf
Liu Y, Kuksenok O, He X, Aizenberg M, Aizenberg J, Balazs AC. Harnessing Cooperative Interactions between Thermoresponsive Aptamers and Gels To Trap and Release Nanoparticles. ACS Appl. Mater. Interfaces. 2016;8 :30475-30483.Abstract

We use computational modeling to design a device that can controllably trap and release particles in solution in response to variations in temperature. The system exploits the thermoresponsive properties of end-grafted fibers and the underlying gel substrate. The fibers mimic the temperature-dependent behavior of biological aptamers, which form a hairpin structure at low temperatures (T) and unfold at higher T, consequently losing their binding affinity. The gel substrate exhibits a lower critical solution temperature and thus, expands at low temperatures and contracts at higher T. By developing a new dissipative particle dynamics simulation, we examine the behavior of this hybrid system in a flowing fluid that contains buoyant nanoparticles. At low T, the expansion of the gel causes the hairpin-shaped fibers to extend into the path of the fluid-driven particle. Exhibiting a high binding affinity for these particles at low temperature, the fibers effectively trap and extract the particles from the surrounding solution. When the temperature is increased, the unfolding of the fiber and collapse of the supporting gel layer cause the particles to be released and transported away from the layer by the applied shear flow. Since the temperature-induced conformational changes of the fiber and polymer gel are reversible, the system can be used repeatedly to “catch and release” particles in solution. Our findings provide guidelines for creating fluidic devices that are effective at purifying contaminated solutions or trapping cells for biological assays.

2016_liu_etal_acs.pdf
Juthani N, Howell C, Ledoux H, Sotiri I, Kelso S, Kovalenko Y, Tajik A, Lin JJ, Sutton A, Aizenberg J. Infused polymers for cell sheet release. Scientific Reports. 2016;6 :26109.Abstract

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.

2016_juthani_etal_scientificreports.pdf
Hu Y, You J-O, Aizenberg J. Micropatterned Hydrogel Surface with High-Aspect-Ratio Features for Cell Guidance and Tissue Growth. ACS Appl. Mater. Interfaces. 2016;8 :21939-21945.Abstract

Surface topography has been introduced as a new tool to coordinate cell selection, growth, morphology, and differentiation. The materials explored so far for making such
structural surfaces are mostly rigid and impermeable. Hydrogel, on the other hand, was proved a better synthetic media for cell culture because of its biocompatibility, softness, and high permeability. Herein, we fabricated a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel substrate with high-aspectratio surface microfeatures. Such structural surface could effectively guide the orientation and shape of human mesenchymal stem cells (HMSCs). Notably, on the flat hydrogel surface, cells rounded up, whereas on the microplate patterned hydrogel surface, cells elongated and aligned along the direction parallel to the plates. The microplates were 2 μm thick, 20 μm tall, and 10−50 μm wide. The interplate spacing was 5−15 μm, and the intercolumn spacing was 5 μm. The elongation of cell body was more pronounced on the patterns with narrower interplate spacing and wider plates. The cells behaved like soft solid. The competition between surface energy and elastic energy defined the shape of the cells on the structured surfaces. The soft permeable hydrogel scaffold with surface structures was also demonstrated as being viable for longterm cell culture, and could be used to generate interconnected tissues with finely tuned cell morphology and alignment across a few centimeter sizes.

2016_hu_etal_acs.pdf
Utech S, Bley K, Aizenberg J, Vogel N. Tailoring re-entrant geometry in inverse colloidal monolayers to control surface wettability. J. Mater. Chem. 2016;4 :6853-6859.Abstract

Controlling the microscopic wetting state of a liquid in contact with a structured surface is the basis for the design of liquid repellent as well as anti-fogging coatings by preventing or enabling a given liquid to infiltrate the surface structures. Similarly, a liquid can be confined to designated surface areas by locally controlling the wetting state, with applications ranging from liquid transport on a surface to creating tailored microenvironments for cell culture or chemical synthesis. The control of the wetting of a low-surfacetension liquid is substantially more difficult compared to water and requires surface structures with overhanging features, known as re-entrant geometries. Here, we use colloidal self-assembly and templating to create two-dimensional nanopore arrays with tailored re-entrant geometry. These pore arrays, termed inverse monolayers, are prepared by backfilling a sacrificial colloidal monolayer with a silica sol–gel precursor material. Varying the precursor concentration enables us to control the degree to which the colloids are embedded into the silica matrix. Upon calcination, nanopores with different opening angles result. The pore opening angle directly correlates with the re-entrant curvature of the surface nanostructures and can be used to control the macroscopic wetting behavior of a liquid sitting on the surface structures. We characterize the wetting of various liquids by static and dynamic contact angles and find correlation between the experimental results and theoretical predictions of the wetting state based on simple geometric considerations. We demonstrate the creation of omniphobic surface coatings that support Cassie–Baxter wetting states for liquids with low surface tensions, including octane (g ¼ 21.7 mN m1). We further use photolithography to spatially confine such low-surface-tension liquids to desired areas of the substrate with high accuracy.

2016_utech_etal_.pdf
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. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2016;113 (42) :11676-11681. Publisher's VersionAbstract

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.

pnas-2016-sunny-1605272113.pdf
Grinthal A, Noorduin W, Aizenberg J. A Constructive Chemical Conversation. American Scientist [Internet]. 2016;104 (4) :228-235. Publisher's VersionAbstract

Using simple ingredients and processing, the authors discuss how they create vastly complex three-dimensional structures that assemble themselves.

Shillingford C, Russell CW, Burgess IB, Aizenberg J. Bioinspired Artificial Melanosomes As Colorimetric Indicators of Oxygen Exposure. ACS Appl. Mater. Interfaces. 2016;8 (7) :4314-4317.Abstract

Many industries require irreversibly responsive materials for use as sensors or detectors of environmental exposure. We describe the synthesis and fabrication of a nontoxic surface coating that reports oxygen exposure of the substrate material through irreversible formation of colored spots. The coating consists of a selectively permeable rubber film that contains the colorless organic precursors to darkly pigmented synthetic melanin. Melanin synthesis within the film is triggered by exposure to molecular oxygen. The selectively permeable rubber film regulates the rate of oxygen diffusion, enabling independent control of the sensitivity and response time of the artificial melanosome, while preventing leaching of melanin or its precursors.

bioinspired_melanosomes.pdf
Phillips KR, England GT, Sunny S, Shirman E, Shirman T, Vogel N, Aizenberg J. A colloidoscope of colloid-based porous materials and their uses. Chem. Soc. Rev. 2016;45 (2) :281-322. ChemSocRev2015.Phillips.pdf
Park K-C, Kim P, Grinthal A, He N, Fox D, Weaver JC, Aizenberg J. Condensation on slippery asymmetric bumps. Nature. 2016;531 :78-82. Nature2016_Parketal.pdf
Kreder MJ, Alvarenga J, Kim P, Aizenberg J. Design of anti-icing surfaces: smooth, textured or slippery?. Nature Reviews Materials. 2016;1 :1-15. NatRevMats2016.Krederetal.pdf

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