Composite Multicellular Spheroids Containing Fibers with Pores and Epigallocatechin Gallate (EGCG) Coating on the Surface for Enhanced Proliferation of Stem Cells

Abstract

Multicellular spheroids are formed by strong cell-cell and cell-extracellular matrix interactions and are widely utilized in tissue engineering for therapeutic treatments or ex vivo tissue modeling. However, diffusion of oxygen into the spheroid gradually decreases, forming a necrotic core. In this study, polycaprolactone (PCL) fibers with pores and epigallocatechin gallate (EGCG) coating on their surface to provide a structural framework within the spheroids and investigated their ability to mitigate diffusional limitation and control over the proliferation of human adipose-derived stem cells (hADSCs) is engineered. The DNA content of composite spheroids prepared from fibers and hADSCs decreased in unadjusted cells (1224 ± 134 ng), in those with fibers with a smooth surface (SF) (1447 ± 331 ng), and in those EGCG-coated with SF (E-SF) (1437 ± 289 ng). Cells with fibers with pores on the surface (PF) (2020 ± 32 ng) and those with EGCG-coated PF (E-PF) (1911 ± 80 ng) increased after 7 days of culture, with a significantly greater number of proliferating cells (29 ± 8% and 30 ± 8%, respectively). These results indicate that physical modification through the formation of pores on the fiber surface alleviates diffusion limitation of composite spheroids, playing a dominant role over chemical modification.

Biofabrication of 3D adipose tissue via assembly of composite stem cell spheroids containing adipo-inductive dual-signal delivery nanofibers

“…In our previous research, we successfully generated hADSC spheroids incorporating ECM-mimicking nanofibers that served as an internal structural framework. This framework effectively alleviated diffusion limitation through the pore spaces, ensuring maintenance of a spherical shape without collapse [41]. Homogeneous distribution of nanofibers and hADSCs was observed throughout the spheroids (figure 4(d)) via SEM examination of cross-sectioned samples (figure 4(e)).…”