Introduction Pancreatic cancer remains a formidable challenge, with 3D cell culture offering a more physiologically relevant model than traditional 2D systems. This study compares how two common scaffold-free 3D platforms— Poly(2-hydroxyethyl methacrylate) (Poly-HEMA or PH) coated plates and ultra-low attachment (ULA) plates—influence spheroid formation, drug sensitivity to gemcitabine, and invasion dynamics in three pancreatic cancer…