Matrix-Metalloproteinase-Responsive Gene Delivery Surface for Enhanced in Situ Endothelialization

Although blood-contacting medical devices have been widely used in the biomedical field, their low endothelialization seriously limits their treatment success. Gene transfection can enhance the proliferation and migration of endothelial cells (ECs) in culture, yet using this technology to realize surface endothelialization still faces great challenges. Herein, we developed a matrix metalloproteinase (MMP) responsive gene delivery surface for in situ smart release of genes from the biomaterial surface upon EC attachment and adhesion. The released genes induced by ECs can, in turn, effectively transfect ECs and enhance the surface endothelialization. An MMP-responsive gene delivery surface (Au-MCP@NPs) was constructed by immobilizing gene complex nanoparticles (NPs) onto a Au surface with MMP-cleavable peptide (MCP) grafted via biotin-avidin interaction. The Au-MCP@NP surface was demonstrated to responsively release NPs under the action of MMPs. More importantly, ECs were effectively transfected on this surface, leading to enhanced proliferation/migration in vitro. The in situ surface endothelialization was evaluated via implanting Au-MCP@NPs into rat aortas. The in vivo results demonstrated that this smart Au-MCP@NP surface could lead to the localized upregulation of ZNF580 protein and accelerate in situ endothelialization. This smart MMP-responsive gene delivery surface provided a promising and powerful strategy for enhanced in situ endothelialization of blood-contacting medical devices.