An albumin-armed fibronectin fragment assembly on stents enables immune evasion, thrombosis prevention, and self-adaptive vascular cell selectivity

Reconstruction of a healthy endothelium following stent implantation is critical for enhancing vascular healing process. Surface engineering of stents with endothelial cell (EC)-selective molecules represents one of the most effective strategies to promote re-endothelialization. However, the adsorption of blood components accompanied by stenting inevitably mask the surface-modified bioactive molecules, leading to a reduction or alteration in the EC selectivity. Herein, we develop a serum albumin (SA)-armed, extracellular-matrix-derived, EC-selective peptide (i.e., REDV) (REDV-SA) self-assembling amyloid-like coating to address this issue. Our results show that the intrinsic biological properties of SA endow the REDV-SA-functionalized stents with immune escape capabilities and resistance to the adsorption of blood components, thereby creating a favorable microenvironment for REDV to exhibit its high EC selectivity. Of particular significance is the adaptive synergy between SA and REDV, which significantly reinforces EC selectivity by inhibiting smooth muscle cell (SMC) adhesion and preferentially promoting EC over SMC migration. Owing to its high EC selectivity, the stent functionalized with REDV-SA coating achieves nearly complete endothelial coverage within one week in vivo , markedly reduces inflammation, and effectively inhibits neointimal hyperplasia, implying great application potential in vascular implants. The albumin-armed fibronectin fragment self-assembling amyloid-like coating not only endows the vascular stents with immune escape capabilities and resistance to the adsorption of blood components, but also reinforces endothelial cell (EC) selectivity by inhibiting smooth muscle cell (SMC) adhesion and preferentially promoting EC over SMC migration, enabling rapid endothelization in vivo . • An albumin-armed REDV amyloid-like self-assembling coating was constructed to reduce protein-corona masking and maintain endothelial selectivity on stent surfaces. • Albumin-REDV adaptive synergy confers immune evasion, inhibits SMC adhesion, and drives EC-preferential migration and re-endothelialization. • REDV-SA-functionalized stents accelerate re-endothelialization and inhibit neointimal hyperplasia, mitigating in-stent restenosis.