The 3D World of Spheroids: Searching for an Optimal Method of Fabricating Pro-Reparative Cardiospheres

This study evaluated how spheroid fabrication conditions influence the structure and reparative potential of cardiospheres derived from cardiac explant-derived cells. The authors compared cardiospheres formed in ultra-low attachment (ULA) U-well plates versus those assembled on poly-D-lysine (PDL)-coated plates, assessing differences in morphology, extracellular matrix organization, cellular features, and pro-angiogenic activity. The two fabrication approaches produced distinct spheroid phenotypes, including differences in compactness and matrix deposition, which were associated with altered functional outputs relevant to regenerative applications. Overall, the work highlights fabrication method as a key design variable that can tune cardiosphere mechanics and downstream reparative performance.