"Synergistic anticoagulant and endothelial regeneration strategy" based on mussel-inspired phospholipid copolymer coating and bioactive zeolitic imidazolate frameworks-90 to maintain the patency of CoCr stent

Int J Biol Macromol. 2024 Nov;280(Pt 2):135842. doi: 10.1016/j.ijbiomac.2024.135842. Epub 2024 Sep 19.

Abstract

Given the risks of poor patient compliance and bleeding associated with current dual antiplatelet therapies, it is urgent to develop the next generation of cardiovascular stents with anticoagulation and rapid endothelialization capabilities. Inspired by the prominent bioactivity and bioavailability of zeolitic imidazolate framework-90 (ZIF-90) in driving endothelial cell (EC) morphogenesis, this research proposes a "synergistic anticoagulant and endothelial regeneration strategy" depending on mussel-inspired phospholipid copolymer (MIPC) and ZIF-90. Depending on the copolymerization of the catechol with dopamine (Dopa) monomers, Dopa/MIPC coating was immobilized on the surface of CoCr via a one-pot process for resisting the initial thrombosis induced by platelets and fibrinogen. Meanwhile, ZIF-90 was loaded on the coating via coordination effect, aiming to accelerate the proliferation and migration of ECs. Compared with CoCr, the well-designed CoCr-Dopa/MIPC@ZIF-90 not only reduced fibrinogen adhesion by approximately 40 % and platelet adhesion by almost 55 %, but also promoted the proliferation and migration of ECs significantly in vitro. Furthermore, the blood flow velocity of CoCr-Dopa/MIPC@ZIF-90 stent was similar to natural aorta and ECs coverage on it was greatly strengthened after 30 days in a rat aorta vascular stent implantation model. Collectively, CoCr-Dopa/MIPC@ZIF-90 exhibited obvious superiority in reducing the formation of thrombus and promoting endothelial regeneration, which might meet the high requirement for the next generation of vascular stent.

Keywords: Anticoagulant coating; CoCr vascular stents; Endothelial regeneration; Mussel-inspired phospholipid copolymer; Zeolitic imidazolate framework-90.

MeSH terms

  • Animals
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology
  • Bivalvia* / chemistry
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / pharmacology
  • Dopamine / chemistry
  • Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Phospholipids* / chemistry
  • Platelet Adhesiveness / drug effects
  • Polymers / chemistry
  • Rats
  • Regeneration / drug effects
  • Stents*
  • Thrombosis / prevention & control
  • Zeolites / chemistry
  • Zeolites / pharmacology

Substances

  • Phospholipids
  • Zeolites
  • Anticoagulants
  • Polymers
  • Imidazoles
  • Dopamine
  • Coated Materials, Biocompatible