3D-Printed poly-є-caprolactone (PCL)-scaffolds are safe for cell support, but their hydrophobicity, bioinertness, and smooth surface limits bioactive/biomimetic performance.This can be overcome by providing biophysicochemical and biomechanical signals using amine (NH2) or carboxyl (COOH)-surface functionalization via wet-chemical treatment or plasma-assisted modification, but the alteration extent and hence bone-cell activity is unknown. We aimed to investigate the influence of NH2 or COOH-surface functionalization via wet-chemical treatment or plasma-assisted modification on biophysicochemical and biomechanical properties of 3D-printed PCL-scaffolds and osteogenic activity. In PCL/NH2 and PCL/COOH scaffolds, only wet-chemical treatment increased void size and surface-roughness, but both treatments reduced water contact angle. Wet-chemical treatment decreased, but plasma-assisted modification increased the elastic modulus. Finite-element modeling revealed that in all scaffolds, maximum von Mises stress under 2% compression-strain did not surpass yield stress for bulk material, indicating excellent mechanical stability and fracture resistance. Wet-chemical treatment and plasma-assisted modification increased pre-osteoblast proliferation, alkaline phosphatase activity, and mineral deposition. Wet-chemical treatment increased Fgf2 mRNA, while both treatments increased Cox2 mRNA. Only wet-chemical treatment increased collagen production. In conclusion, NH2 and COOH-surface functionalization of 3D-printed PCL-scaffolds via wet-chemical treatment was superior to plasma-assisted modification in enhancing osteogenic activity, and is therefore more promising for in vivo bone formation.