The creation of artificial organs turned into tetris

Oleg Lischuk, N+1

Taiwanese scientists have developed a universal platform for creating complex three-dimensional hydrogel structures functionally similar to biological structures or representing metamaterials with new properties. The results of the work are published in the journal Science Advances (Chiang et al., Constructing 3D heterogenic hydrogels from electrically manipulated prepolymer droplets and crosslinked microgels).

Three-dimensional hydrogel biological tissues, or metamaterials, are created from cross-linked heterogeneous structural elements (microgels) in which functional particles or molecules are embedded. For the production of microgels with a given structure and properties, various methods are used, such as emulsion polymerization, microforming, photolithography, microfluidic assembly and others. All these methods have limitations related either to the shape and material of the resulting microgels, or to the complexity or high cost of consumables and equipment. Further assembly of structural elements into a three-dimensional functional hydrogel also presents difficulties: self-assembly is practically not applicable to architectures of heterogeneous elements, manual assembly is time-consuming, and robotic requires high-precision optical or magnetic control of micro robots.

Employees of the National Jiao Tong University and the National Taiwan University have developed an electro-microfluidic platform in which the creation of microgels of different compositions and their subsequent assembly into a hydrogel occur in a liquid medium and are controlled by electric wetting (it directs the charged liquid to an electrode with a suitable coating) and dielectrophoresis (it causes the movement of uncharged particles or living cells under the action of an inhomogeneous electric field).

To do this, materials with different properties (dispersed particles, soluble molecules, living cells, and others) are placed in tanks, mixed with a solvent containing a polymerizable gel base and a dye, dosed and placed in a certain area of the platform using a network of electrodes and held in it. The multidirectional action of electric wetting and dielectrophoresis allows, in accordance with a given program, to control the location of droplets of materials on the platform, move them (as when playing tetris or tag), change their shape and structure and mix with each other. When a given configuration is reached, the droplets of materials are cured by light of a given frequency to form flat microgels with a size of 1 × 1x0.1 millimeter.

Fabrication of a complex hydrogel structure from different materials (designated W, R, B and G)
and their combinations (fig. from an article in Science Advances).

Then the microgels are arranged in the desired configuration in one or more layers (the distance between the upper and lower walls of the platform is 0.3 millimeters) and they are stitched into the final hydrogel architecture.

The developed platform allows manipulating objects of different sizes (from micrometer functional particles to millimeter microgels), in different phases (liquid and solid) and with different properties (conductors or dielectrics, cross-linked by light, chemically or temperature).

As a demonstration of the platform's capabilities, its developers fabricated with its help a hydrogel analogue of the heart muscle from living cardiomyocytes (cardiac muscle cells) and fibroblasts (connective tissue cells). In 48 hours, the cells formed clusters that spontaneously contracted with a frequency of 73 to 91 beats per minute (this corresponds to a normal heart rhythm without regulation by the autonomic nervous system). Moreover, the proportion of cardiomyocytes was more than 50 percent versus 27.8 percent on a standard multipath tablet with a nutrient medium.

According to the developers, they expect that their electro-microfluidic platform will become a common technique for creating complex three-dimensional hydrogel structures, including artificial organs.

Many teams are working on the development of technologies for creating artificial organs both for the purpose of conducting experiments and for implantation to patients. For example, recently scientists from Harvard printed a heart muscle on a 3D printer, which registers its contractions by itself. You can read about how artificial organs are created in our material.

Portal "Eternal youth" http://vechnayamolodost.ru  28.10.2016