Polyphenol-Reinforced Glycocalyx-Like Hydrogel Coating Induced Myocardial Regeneration and Immunomodulation.

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.

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

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 Zn2+ 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.

Polyphenol-mediated sandwich-like coating promotes endothelialization and vascular healing.

Drug-eluting stents have become one of the most effective methods to treat cardiovascular diseases. However, this therapeutic strategy may lead to thrombosis, stent restenosis, and intimal hyperplasia and prevent re-endothelialization. In this study, we selected 3-aminophenylboronic acid-modified hyaluronic acid and carboxylate chitosan as polyelectrolyte layers and embedded an epigallocatechin-3-gallate-tanshinone IIA sulfonic sodium (EGCG-TSS) complex to develop a sandwich-like layer-by-layer coating. The introduction of a functional molecular EGCG-TSS complex improved not only the biocompatibility of the coating but also its stability by enriching the interaction between the polyelectrolyte coatings through electrostatic interactions, hydrogen bonding, π-π stacking, and covalent bonding. We further elucidated the effectiveness of sandwich-like coatings in regulating the inflammatory response, smooth muscle cell growth behavior, stent thrombosis and restenosis suppression, and vessel re-endothelialization acceleration via in vivo and in vitro. Conclusively, we demonstrated that sandwich-like coating assisted by an EGCG-TSS complex may be an effective surface modification strategy for cardiovascular therapeutic applications.

An organic selenium and VEGF-conjugated bioinspired coating promotes vascular healing.

The introduction of drug-eluting stents (DESs) have yield a significant reduction in the incidence of re-stenosis, however, challenges remain including incomplete healing of the endothelium, inflammatory response and thrombogenesis at the site of vascular wall injury. Here, we developed a novel stent with polyphenol-polyamine surface combining the biological functions of nitric oxide gas and VEGF, selectively promoting the proliferation and migration of endothelial cells while suppressing smooth muscle cells. Compared with bare PLLA stents and traditional DESs, the functionalized stents enhanced vascular healing through remarkable inhibiting intimal hyperplasia and occurrence of thrombosis, accelerating the in-situ endothelium repair. Moreover, it showed a down-regulation of injury vascular inflammation response and reduction of the vessel wall injury in New Zealand Rabbits after 1- and 3-month implantation.

A Polyphenol-Network-Mediated Coating Modulates Inflammation and Vascular Healing on Vascular Stents.

Localized drug delivery from drug-eluting stents (DESs) to target sites provides therapeutic efficacy with minimal systemic toxicity. However, DESs failure may cause thrombosis, delay arterial healing, and impede re-endothelialization. Bivalirudin (BVLD) and nitric oxide (NO) promote arterial healing. Nevertheless, it is difficult to combine hydrophilic signal molecules with hydrophobic antiproliferative drugs while maintaining their bioactivity. Here, we fabricated a micro- to nanoscale network assembly consisting of copper ion and epigallocatechin gallate (EGCG) via π-π interactions, metal coordination, and oxidative polymerization. The network incorporated rapamycin and immobilized BVLD by the thiol-ene "click" reaction and provided sustained rapamycin and NO release. Unlike rapamycin-eluting stents, those coated with the EGCG-Cu-rapamycin-BVLD complex favored competitive endothelial cell (EC) growth over that of smooth muscle cells, exhibited long-term antithrombotic efficacy, and attenuated the negative impact of rapamycin on the EC. In vivo stent implantation demonstrated that the coating promoted endothelial regeneration and hindered restenosis. Therefore, the polyphenol-network-mediated surface chemistry can be an effective strategy for the engineering of multifunctional surfaces.