Ang-1-releasing RADA16 peptide coating modulates inflammation and suppresses smooth muscle proliferation

Post-stent implantation vascular complications, including impaired re-endothelialization and persistent inflammation, frequently lead to late-stage thrombosis and in-stent restenosis. Current approaches often fall short in simultaneously promoting healing and suppressing detrimental cell proliferation. Angiopoietin-1 (Ang-1) is a crucial regulatory molecule for vascular homeostasis, coordinating endothelial regeneration and vascular stabilization. Leveraging self-assembling peptides offers a promising avenue for targeted vascular therapy to address these complex issues.

Researchers engineered a RADA16 peptide-based coating loaded with Ang-1 to mimic the unbound state of endogenous Ang-1. The study evaluated the coating's ability to modulate inflammatory responses, promote re-endothelialization, and accelerate vascular repair. They assessed sustained Ang-1 release, cytocompatibility, and effects on human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs). Macrophage (MA) proliferation and pro-inflammatory cytokine secretion (IL-6, TNF-α) were also measured, alongside macrophage polarization towards the M2 phenotype.

The Ang-1-loaded RADA16 coating demonstrated sustained Ang-1 release for more than 14 days, confirming its potential for prolonged therapeutic action. Both the plain peptide coating and the Ang-1-loaded version exhibited excellent cytocompatibility, indicating low toxicity.

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 the secretion of pro-inflammatory cytokines, specifically interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Importantly, both the plain peptide coating and the Ang-1-loaded coating promoted the polarization of macrophages toward the M2 phenotype, which is crucial for inflammation resolution and tissue repair. These findings collectively show the Ang-1-loaded coating creates an immune-favorable microenvironment conducive to vascular repair.