Mass Production of Cell‐Laden Calcium Alginate Particles with Centrifugal Force

Abstract

This paper describes a centrifuge-based device for oil-free and mass production of calcium-alginate (Ca-alginate) particles. The device is composed of four components: a tank with a glass capillary for forming sodium alginate droplets, a collecting bath with calcium chloride (CaCl ) solution, a waste liquid box, and a bypass channel bridged between the collecting bath and the waste liquid box. When the device is centrifuged, extra CaCl solution in the collecting bath is delivered to the waste liquid box to maintain the appropriate liquid level of CaCl solution for the production of monodisperse Ca-alginate particles. The proposed device enables oil-free production of over 45 000 uniformly sized Ca-alginate particles in a single 240 s process, whereas using the conventional method with only a glass capillary, ≈1000 particles are formed within the same processing time. Because of the high biocompatibility of the oil-free process, the device is applicable to cell encapsulation in Ca-alginate particles with high cell viability, as well as the formation of a macroscopic 3D cellular structure using Ca-alginate particles covered with cells as assembly modules. These results suggest that the device can be a useful tool for preparing experimental platforms in biomedical and tissue engineering fields.

Biofabrication strategies for 3D in vitro models and regenerative medicine

“…Point-shaped cell-laden structures are easily prepared by culturing cells with hydrogel beads made of alginate 108,109 , PEG 110,111 or collagen 112,113 . Such structures are fabricated using microfluidic devices with T junction, flow-focusing and nozzleshaped microchannels.…”

“…Moulding is a popular method for the assembly of cell-laden beads. In this method, the beads are packed into a mould and integrated through cell adhesion, resulting in the construction of millimetre to centimetre-sized tissues with specific shapes defined by the shape of the mould 108,111,112,114,115 (FIG. 5a).…”

Formation of Branched and Chained Alginate Microfibers Using Theta-Glass Capillaries

“…Alginate microfibers have been attractive materials for biomedical applications such as cell and drug encapsulation [ 1 , 2 , 3 ], scaffolds for cell culture [ 4 , 5 , 6 ], and channel formation as sacrificial templates [ 7 , 8 , 9 ] because of their biocompatibility, biodegradability, and mechanical flexibility [ 1 ]. There have been two main methods to form the alginate microfibers: electrospinning and microfluidic spinning [ 10 , 11 , 12 ].…”

Development of Cell Spheroids by Advanced Technologies

“…[18][19][20][21][22] The second category is scaffold-free culture system, including culturing cells in suspension, on antiadhesion substrates, in hanging drops, etc. [23][24][25][26][27][28][29][30] In addition to the above commonly used methods, spheroids can also be prepared by centrifugation and hydrophilic-hydrophobic microarrays based on surface wettability technology. [31][32][33][34][35] Recently, many emerging strategies based on microfluidics have been developed that possess the capability to produce abundant cell spheroids with more uniform size.…”