This study investigates the use of biodegradable polymer scaffolds to promote the growth and differentiation of human embryonic stem (hES) cells into complex, viable 3D tissues. The researchers found that hES cells can be induced to differentiate into various embryonic tissues, such as neural, cartilage, and liver, when grown on supportive 3D environments like poly(lactic-co-glycolic acid)/poly(lactic acid) polymer scaffolds. Growth factors like retinoic acid, transforming growth factor β, activin-A, and insulin-like growth factor were used to direct the differentiation and organization of hES cells. These constructs, when transplanted into severe combined immunodeficient mice, maintained their viability, expressed specific human proteins, and integrated with the host vasculature. The study demonstrates the potential of this approach for creating viable human tissue structures for therapeutic applications and provides insights into cell and developmental biology.This study investigates the use of biodegradable polymer scaffolds to promote the growth and differentiation of human embryonic stem (hES) cells into complex, viable 3D tissues. The researchers found that hES cells can be induced to differentiate into various embryonic tissues, such as neural, cartilage, and liver, when grown on supportive 3D environments like poly(lactic-co-glycolic acid)/poly(lactic acid) polymer scaffolds. Growth factors like retinoic acid, transforming growth factor β, activin-A, and insulin-like growth factor were used to direct the differentiation and organization of hES cells. These constructs, when transplanted into severe combined immunodeficient mice, maintained their viability, expressed specific human proteins, and integrated with the host vasculature. The study demonstrates the potential of this approach for creating viable human tissue structures for therapeutic applications and provides insights into cell and developmental biology.