Magnetic assembly of microfluidic spun alginate microfibers for fabricating three-dimensional cell-laden hydrogel constructs

摘要

Microfluidic devices employed as "printing" head provide a mild condition to fabricate cell-laden hydrogel modules for three-dimensional (3D) assembly to create cellular constructs. However, because of the poor controllability of hydrogels and unstable microfluidic fabrication process, it remains a challenge to fabricate morphologically accurate structures to mimic in vivo tissues, which hinders the building of in vitro models of organs. In this paper, we combine a magnetic-driven strategy into a microfluidic "printing" method to handle this challenge. To enhance the controllability, we encapsulate magnetic nanoparticles (MNPs) into cell-laden alginate hydrogel microfibers and then magnetically assemble these microfibers on the surface of designed support models. To keep a continuous spinning process, we immerse the spinning orifice of microfluidic device into phosphate-buffered saline filled in a Petri dish to eliminate the influence of droplets generated during microfibers ejection. Meanwhile, a dextran flow impulse is employed to prevent the blockage of microchannels. Interestingly, this impulse can achieve to temporarily cease the spinning process. Moreover, an optimized magnetic assembly is achieved by considering both the assembling area on a ring magnet and the MNPs concentration in microfibers. After the test of cell survival, a high cell viability of 97.2 % can be confirmed in assembled structures, which indicates that our method allows a biocompatible assembly of cell-laden hydrogels to build macroscopic 3D cellular structures similar to tissues observed in vivo.