Screening and functional validation of groove structures differentially regulating endothelial/smooth muscle cell behavior.

Drug-eluting stents inhibit smooth muscle cell proliferation but simultaneously impede endothelial repair, leaving restenosis risk still prominent. Surface microstructures, as a physical modulation approach, hold promise for improving cell selectivity; however, a systematic study on how to select the optimal topography from multiple configurations to precisely balance the behaviors of two cell types is lacking. In this work, we designed six microstructures and performed a systematic screening. We found that groove structure V (with a groove width of ~3.73 μm, depth of ~1.00 μm, and ridge width of ~2.33 μm) not only significantly promoted the proliferation of human coronary artery endothelial cells (HCAECs) but also maximally inhibited the excessive proliferation of human coronary artery smooth muscle cells (HCASMCs), thereby achieving the greatest differentiation in proliferative responses between the two cell types and enabling a differential regulation favoring endothelialization. After transferring this optimal structure onto nickel‑titanium alloy surfaces, we further verified that it enhanced the adhesion, migration, and competitive growth of human umbilical vein endothelial cells (HUVECs) and induced necrosis of smooth muscle cells (HUVSMCs), significantly accelerating the re-endothelialization process. By combining microstructure screening with nickel‑titanium alloy application, this study demonstrates that metallic surface topography can actively modulate differential cellular responses, providing a new basis for the biocompatible design of vascular stents.