Construction of gigantic highly-porous microcarriers as a three-dimensional cell culture platform

Abstract

3D cell carriers with porous structures have the potential to promote cellular interactions and extracellular matrix remolding, making it a promising strategy to investigate the complex mechanisms behind drug treatments for tumors. Nevertheless, the applicability of currently reported porous microcarriers is still limited by the relatively small size and poor pore interconnectivity. Herein, a well-defined gigantic highly-porous poly(lactic-co-glycolic acid) (PLGA) microsphere (named LPMs) fabrication platform is reported. Utilizing this “LPMs” platform, arrays of well-uniform particles with sizes up to approximately 1000 µm are prepared in an orderly and controlled manner. The preparation matrix and crucial parameters affecting the particle size and pore size were established through extensive single-factor screening. It was also found that the loading of human gastric cancer cells MGC-803 to the LPMs cell carriers was facilitated not only by the increased pore size, but the particle size should also be enlarged along with the increased pore size. Through surface modification of gelatin on LPMs, cell loading could be dramatically enhanced, and microtissue-like structures were formed through cross-linking LPMs under extended 3D culture time. Under the guidance of these findings, we successfully constructed massive tumor cell carriers with 1000 µm LPMs, a preliminary prototype of a massive tumor tissue mimic. Together, the fabrication of these gigantic highly-porous microcarriers possibly allows for the high-efficiency 3D cell culture and represents the attractive potential of the construction of artificial tumor tissue models with massive and multiple-type cells.