Engineering Immunomodulatory Stents Using Zinc Ion–Lysozyme Nanoparticle Platform for Vascular Remodeling

Abstract

Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn 2+ ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal−polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.

Effects of scutellarin on the mechanism of cardiovascular diseases: a review

“…In recent years, the eNOS/cGMP/PKG signal pathway has been considered an important target for therapies such as regulating blood pressure, attenuating IR injury, and delaying heart failure ( Anwar et al, 2017 ; Kolijn et al, 2021 ; Park et al, 2022 ). Additionally, the eNOS/cGMP/PKG signal route is crucial for controlling blood pressure and vascular endothelial function ( Zhang et al, 2023 ).…”