Spheroid Sheets: A Scalable Platform for Producing Tissue Membrane Constructs

Research Overview

Bottom-up tissue engineering with cell spheroids recapitulates native cell–cell and cell–matrix interactions, and spheroids have been used to build cartilage, bone, cardiac muscle, intestine, and neural tissue. But existing ways of assembling spheroids — mold casting, hydrogel bioprinting, needle arrays — either give poor control over final geometry or fail to scale.

This protocol describes a robust, scalable method for assembling spheroids into a thin, planar sheet: spheroids are sandwiched between two flexible meshes held in a frame, which promotes uniform fusion while preserving nutrient exchange and making the construct easy to handle. The method is demonstrated by producing thin cartilage tissue from human mesenchymal stem cells.