Angiogenic factors secreted from human ASC spheroids entrapped in an alginate-based hierarchical structure via combined 3D printing/electrospinning system.

Human adipose-derived stem cell spheroids have been widely used in the treatment or regeneration of damaged skin tissues, and their success is believed to be due in part to angiogenic factors released from the spheroids. To achieve the sustained release of bioactive components from implanted spheroids within a defective area, the use of a biocompatible scaffolding biomaterial is required. In this study, we developed an alginate-based scaffolding structure, which was processed using three-dimensional printing and electrospinning for use as a spheroid-entrapping structure. A micro-sized alginate strut and electrospun alginate nanofibers functioned not only to firmly entrap the spheroids, but also to enable the stable release of various angiogenic and wound healing-related factors. We also demonstrated the function of these factors using a tube-forming assay and found that conditioned media from the spheroid-scaffold group improved capillary-like structure formation in human umbilical vein endothelial cells compared to the single cell-scaffold group. Our results suggest that this spheroid-entrapping alginate hybrid structure could represent a new platform for stem cell therapy using spheroid transplantation.