Rosuvastatin- and Heparin-Loaded Poly(l-lactide- co-caprolactone) Nanofiber Aneurysm Stent Promotes Endothelialization via Vascular Endothelial Growth Factor Type A Modulation.

Abstract

This study explored a new rosuvastatin calcium- and heparin-loaded poly(l-lactide- co-caprolactone) (PLCL) scaffold for covered stents for treating aneurysms. The mechanism of rosuvastatin-induced endothelialization via vascular endothelial growth factor (VEGF)-A elevation was further explored. Rosu50, Rosu75, Rosu100, and phosphate-buffered saline (PBS) nanofibrous scaffolds were fabricated by coaxial electrospinning and observed by electron microscopy. Anticoagulation and pro-endothelialization properties were tested. Sixteen rabbits were selected for an in vivo assay and underwent microsurgery to establish a carotid aneurysm model. The animals were treated with covered stents and followed for 4 months using digital subtraction angiography (DSA), electron microscopy, and histology. Rosuvastatin-treated human umbilical vein endothelial cell (HUVEC) viability, function, and VEGF-A modulation were further studied to elucidate the pro-endothelialization mechanism of rosuvastatin. Our study demonstrates that rosuvastatin and heparin can be incorporated into PLCL nanofibers via electrospinning. Rosu100 nanofiber scaffolds exhibited significant anticoagulation properties. The viability of HUVECs transferred to Rosu100 nanofiber scaffolds was increased significantly. In vivo, DSA revealed that the Rosu100 group had better outcomes than the PBS group. In addition, the Rosu100 stents induced more integrated endothelialization. Further study demonstrated that rosuvastatin promoted HUVEC viability and function in vitro. The effects of rosuvastatin may be attributed to an elevation in VEGF-A. We demonstrated that rosuvastatin- and heparin-loaded PLCL-covered stents show favorable anticoagulation and pro-endothelialization properties in vitro and in vivo in a rabbit aneurysm model. VEGF-A elevation played a crucial role in rosuvastatin-promoted endothelialization. This work provides an additional option for treating cerebral aneurysms with covered stents.