PLLA Composites Combined with Delivery System of Bioactive Agents for Anti-Inflammation and Re-Endothelialization

Pharmaceutics. 2022 Nov 30;14(12):2661. doi: 10.3390/pharmaceutics14122661.

Abstract

The development of a biodegradable vascular scaffold (BVS) for the treatment of cardiovascular diseases (CVDs) still requires some improvement. Among them, re-endothelialization and anti-inflammation are clinically important to restore vascular function. In this study, we proposed a coating system to deliver hydrophilic bioactive agents to BVS using nanoemulsion and drop-casting methods. The poly(L-lactide) (PLLA) scaffold containing magnesium hydroxide (MH) was coated on the surface with bioactive molecules such as polydeoxyribonucleotide (PDRN), L-arginine (Arg, R), and mesenchymal stem cell-derived extracellular vesicles (EVs). PDRN upregulates the expression of VEGF as one of the A2A receptor agonists; and Arg, synthesized into nitric oxide by intracellular eNOS, induces endothelialization. In particular, EVs, which are composed of a lipid bilayer and transfer bioactive materials such as protein and nucleic acid, regulate homeostasis in blood vessels. Such a bioactive agent coating system and its PLLA composite suggest a new platform for the treatment of cardiovascular dysfunction.

Keywords: angiogenesis; arginine; extracellular vesicle; magnesium hydroxide; poly(L-lactide); polydeoxyribonucleotide; vascular regeneration.