The assembly of cell-encapsulated microparticles in a microfluidic system using optically induced dielectrophoretic (ODEP) force for structurally-controllable cartilage tissue engineering

Animal tissues normally have their inherently unique tissue architectures that are biologically meaningful for their tissue functions. Nevertheless, the conventional tissue engineering approaches cannot tailor the structures of an engineered tissue construct. To tackle the technical hurdle, the concept of “bottom-up” tissue engineering holds immense promise, by which an entire engineered tissue construct is fabricated by the assembly of smaller building blocks (e.g. cells-encapsulated microparticles). Although some pioneered studies [1] have been demonstrated such emerging strategy, they have not yet set in motion an evolutionary shift from conventional tissue engineering methods. Thanks to the appropriate dimensional features in a microfluidic system and the techniques of optically induced dielectrophoretic (ODEP) force, the precise manipulation of microparticles can be easily achieved. Briefly, when microparticles with dielectric properties are under an applied electric field, charges can be electrically polarized on the particle surface. The interaction between such induced charges and the applied electric field can generate DEP force. By the control of DEP force, microparticles can be manipulated. The ODEP technique [2], making use of optical images to create virtual electrodes, has attracted considerable interests due to its higher flexibility in terms of operations and applications. In this study, a microfluidic system capable of providing ODEP force for the manipulation and assembly of cell-encapsulated alginate microbeads is proposed (Fig. 1 (a)). In operation, one can use a commercial digital projector to display controllable optical images on the photoconductive material to manipulate the microbeads. By this, a complicated layout of microbeads can be patterned in a manageable manner. The overall experimental setup is schematically illustrated as Fig. 1 (b). To demonstrate that the proposed system can achieve microbead patterning, polystyrene microbeads with various colors were loaded into the system (Fig. 2 (a)). ODEP force was used to sort, separate (Fig. 2 (b)-(c)), and pack (Fig. 2 (d)) the microbeads. For demonstrating the use of the proposed system for structurally-controllable cartilage tissue engineering, chondrocytes-encapsulated alginate microparticles with varied particle size and cell densities were generated using a micro-vibrator, based on our previous work [3]. Three kinds of chondrocytes-encapsulated alginate microparticles were generated as shown in Fig. 3. The manipulation and assembly of them to simulate the chondrocyte distribution in articular cartilage was carried out. Result (Fig. 4) exhibited the cell distribution in the tissue culture construct can be tailored by the proposed system. This study has successfully demonstrated touse ODEP forces to manipulate microparticles in a microfluidic system to assemble a tissueculture construct with a desirable cell distribution. References[1]A.P. McGuigan, M.V. Sefton, Proc. Natl. Acad. Sci. U. S. A, 103., 11461-11466(2006)[2]P.Y. Chiou, A.T. Ohta, M.C. Wu, Nature, 436., 370–372(2005)[3]S.B. Huang, M.H. Wu, G.B. Lee, Sens. Actuator B-Chem., 147., 755-764(2010)