Bioinert Albumin Surface Enables Ultra-High Vascular Cell Selectivity Superior to Specific Binding Ligands

Enhancing the selectivity of endothelial cells (ECs) over smooth muscle cells (SMCs) on material surfaces is critical for improving the prognosis of cardiovascular device implantation, preventing restenosis, and avoiding late-stage thrombosis. However, existing surface modification strategies typically involve specific binding ligands such as antibodies and extracellular matrix peptides to promote EC adhesion, which exhibit low EC selectivity with EC/SMC ratios of less than 10. Herein, we report that an albumin coating, traditionally regarded as a bioinert surface lacking specific recognition functions, achieves unprecedented high EC selectivity with an EC/SMC ratio exceeding 200 in the medium supplemented with 5% fetal bovine serum. Mechanistic investigations reveal that this selectivity is achieved by selectively impeding the adhesion of SMCs, contrasting the traditional approach of using specific ligands to promote EC adhesion selectively. Evaluations in an animal model demonstrated successful inhibition of intimal hyperplasia and the promotion of endothelialization of the modified implants. This facile albumin modification shows potential for enhancing the performance of implantable cardiovascular devices by achieving complete endothelialization.