An Ang-1-releasing self-assembling peptide coating for inflammation modulation and suppression of smooth muscle proliferation

Post-stent implantation vascular complications, primarily characterized by impaired re-endothelialization and persistent inflammatory responses, frequently result in delayed vascular healing and subsequent adverse clinical outcomes, including late-stage thrombosis and in-stent restenosis. Cytokines act as master regulators of vascular repair, coordinating endothelial regeneration, inflammatory responses, and tissue remodeling. Angiopoietin-1 (Ang-1) is a particularly significant regulatory molecule within the vascular system, exerting pleiotropic effects on vascular homeostasis through dual regulation of endothelial regeneration and vascular stabilization. Self-assembling peptide systems, with their unique combination of programmable molecular design and inherent biocompatibility, are revolutionizing targeted vascular therapy development. In this study, we developed an RADA16 peptide-based coating loaded with Ang-1 to mimic the unbound state of endogenous Ang-1, thereby modulating inflammatory responses, promoting re-endothelialization, and accelerating vascular repair. The RADA16 peptide coating enabled sustained Ang-1 release for more than 14 days. Both the peptide coating and Ang-1-loaded peptide coatings exhibited excellent cytocompatibility. The Ang-1 loaded coating significantly enhanced the growth and migration of human umbilical vein endothelial cells (HUVECs) while selectively inhibiting the proliferation of smooth muscle cells (SMCs). Furthermore, the coating effectively suppressed macrophage (MA) proliferation and reduced secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Meanwhile, both PAs coating and PAs-Ang coating promote the polarization of macrophages toward the M2 phenotype, facilitating inflammation resolution and tissue repair. The Ang-1 loaded coating exerting anti-inflammatory effects and creating an immune-favorable microenvironment conducive to vascular repair. The Ang-1-eluting peptide coating exhibited a trifecta of therapeutic effects by selectively promoting endothelial cell proliferation and migration while suppressing inflammatory responses. This multifunctional bioactive coating reveals anti-inflammatory activity, pro-endothelialization capacity, and inhibition of smooth muscle cell hyperplasia. This work offers a novel strategy for cardiovascular biomaterials development, and provides a new surface modification approach for cardiovascular implants.