Preparation of Ascidian-Inspired Hydrogel Thin Films to Selectively Induce Vascular Endothelial Cell and Smooth Muscle Cell Growth

Hydrogel thin films (HTFs), which have multiple functions including hemocompatibility and ability of enhancing growth of endothelia cells (ECs) while suppressing proliferation of smooth muscle cells (SMCs), have garnered intense scientific interest due to their potential applications in the field of blood-contact materials. In the present study, we developed stable, multifunctional HTFs containing multiple functional groups (-SO₃Na, -COONa, -OH, and -NH₂) by layer-by-layer (LbL) self-assembly of a modified sulfonated sodium alginate (SSA) and chitosan (CS), followed by ascidian-inspired post-cross-linking. The prepared HTFs with a 3D porous structure, as revealed by scanning electron microscopy (SEM), maintained outstanding long-term stability. The results of protein adsorption, platelet adhesion and activation, and clotting time confirmed that the hemocompatibility of the HTFs was significantly enhanced compared with the matrix. From the cytocompatibility test, the multiple functional groups at the HTF surface led to remarkable enhancement in human umbilical vein endothelial cell (HUVEC) growth and significant inhibition effects on human umbilical artery smooth muscle cell (HUASMC) proliferation. The ratio of HUVEC to HUASMC increased from 0.25 on the Ti surface to 2.87 on the surface of the HTF with the highest degree of sulfonation (DS). The improved blood compatibility was ascribed to the introduction of the multiple functional groups, and the strongly selective effects on vascular cells were attributed to the synergistic effect of the high degree of sulfonation and the existence of phenolic hydroxyl groups. The unique HTFs prepared in this study, demonstrating excellent hemocompatibility and high selectivity toward vascular cells, may help guide the design of cardiovascular biomaterials for endothelialization.