Controlled formation of polylysinized inner pores in injectable microspheres of low molecular weight poly(lactide-co-glycolide) designed for efficient loading of therapeutic cells

Abstract

This study aimed to develop porous microspheres with a suitable porous structure and mechanical property for cell delivery using a comparatively low molecular weight (MW) poly(lactide-co-glycolide) (PLGA) having a weak mechanical strength and fast degradation rate, which could be potentially used for treatment of corneal endothelial diseases. Porous microspheres of 30 kDa PLGA with different pore sizes were prepared by varying preparation conditions, and the microspheres with mean pore diameters approximately 0.5, 1, 2 and 3 times that of a single green fluorescent protein-expressing human embryonic kidney 293 cell, used as a model cell, were chosen for cell loading study. The microspheres with an average pore diameter two times greater than that of the single cell were found to be the most appropriate for efficient cell loading in the inner pore spaces, along with demonstrating a good mechanical property, injectability and biodegradability. To maximize the cell loading amount in the microspheres, the cell adhesive property of the microspheres and cell loading conditions were optimized, leading to approximately 4.2 times increase in the cell loading amount. The porous microspheres designed using the low MW PLGA hold promise as a delivery system of corneal endothelial cells for regeneration of the corneal endothelium.