Cell Spheroid Formation on the Surface of Multi‐Block Copolymers Composed of Poly(2‐methoxyethyl acrylate) and Polyethylene Glycol

Abstract

Abstract3D structured cells have great drug screening potential because they mimic in vivo tissues better than 2D cultured cells. In this study, multi‐block copolymers composed of poly(2‐methoxyethyl acrylate) (PMEA) and polyethylene glycol (PEG) are developed as a new kind of biocompatible polymers. PEG imparts non‐cell adhesion while PMEA acts as an anchoring segment to prepare the polymer coating surface. The multi‐block copolymers show higher stability in water than PMEA. A specific micro‐sized swelling structure composed of a PEG chain is observed in the multi‐block copolymer film in water. A single NIH3T3‐3‐4 spheroid is formed in 3 h on the surface of the multi‐block copolymers with 8.4 wt% PEG. However, at a PEG content of 0.7 wt%, spheroid formed after 4 days. The adenosine triphosphate (ATP) activity of cells and the internal necrotic state of the spheroid change depending on PEG loading in the multi‐block copolymers. As the formation rate of cell spheroid on low‐PEG‐ratio multi‐block copolymers is slow, internal necrosis of cell spheroid is less likely to occur. Consequently, the cell spheroid formation rate by changing the PEG chain content in multi‐block copolymers is successfully controlled. These unique surfaces are suggested to be useful for 3D cell culture.