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Liquid-Like Solids (LLS™)

A New Class of 3D Culture Medium
Above: A whimsical moon jellyfish comprised of fluorescent nano beads is printed into a bottle of LLS. The supportive bed of hydrogel particles prevents these particles from falling, resulting in a delicate, but mechanically stable, free-form print.  

What Are Liquid-Like Solids?

Aurita’s mission is to develop methods and models that enable physiologically relevant, in vitro, studies of human disease. Culture devices from Aurita are engineered to mimic one of the most ubiquitous environments in the human body: the capillary bed. To this end, our systems leverage a unique class of materials that we call Liquid-Like Solids, or LLS™, which is fundamentally a granular hydrogel material, or microgel.

A fundamental property of solid materials is mechanical stability, which is the reason that bubbles in hand sanitizer, an everyday example of LLS™, won’t rise if they are small enough, and suspended particles will not sink. On the other hand, liquids are defined by their ability to flow and conform to their container, which hand sanitizer certainly does. So how can it be both a solid and a liquid?
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The answer is rather simple: LLS™ is made up of a vast number of individual, small, particles. When stationary, the particles settle in and act like a bulk solid with a finite yield stress, thus allowing for the retention of small bubbles and particles. When shear is applied, the particles swiftly move about and the bulk material flows like a liquid, filling the container it is placed into. These properties make it a perfect material for free-form 3D printing and biofabrication, as no additional support material is required, and for 3D cell culture where the intergranular spaces are perfect channels for motile immune cells and the malleability of the material on even the microscale means tumoroids, spheroids, tissue explants, and the like can grow, expand, and remodel their environment.

Left: A whimsical moon jellyfish comprised of fluorescent nano beads is printed into a bottle of LLS. The supportive bed of hydrogel particles prevents these particles from falling, resulting in a delicate, but mechanically stable, free-form print.  
Above: Astrocytes grown in LLS bioconjugated with Type I Collagen adhere to the surfaces of adjacent particles. Because LLS is essentially water, the particles are completely transparent, allowing cells behind particles to be readily imaged. Transparency is a key feature of LLS, enabling its use in in situ  assays which benefit from high fidelity imaging.

Liquid-Like Solids as a 3D Culture Medium

LLS™ for cell culture is made of polyacrylamide hydrogel particles whose size is set to yield connected interparticle pore spaces which are reminiscent of capillaries. Immune cells can freely navigate through these interparticle spaces, and through the use of Darcy Plates™, perfusion of media feeds cells while simultaneously removing waste, just like a capillary bed. Further functionality is enabled using Bioconjugated LLS™ where surface coatings of ECM proteins on the microgel particles can be added, functional antibodies can be added, or even internal fluorescent tags can be conjugated to allow for visualization and tracking of LLS particles. Our bioconjugation technique yields microgels with defined concentrations of each input, making it one of the only chemically defined 3D culture mediums currently available. The combination of functional LLS™ and Darcy Plates™ for perfusion have supported everything from patient matched immunotherapy studies to high-density cell culture for drug and biologics production.
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Right: Astrocytes grown in LLS bioconjugated with Type I Collagen adhere to the surfaces of adjacent particles. Because LLS is essentially water, the particles are completely transparent, allowing cells behind particles to be readily imaged. Transparency is a key feature of LLS, enabling its use in in situ  assays which benefit from high fidelity imaging.
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