Hybrid Electrospun Rapamycin-Loaded Small-Diameter Decellurized Vascular Grafts Effectively Inhibit Intimal Hyperplasia

Abstract

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular disease, there is a significant demand for small diameter (inner diameter < 6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aortas (DRA). However, histological assessments of the grafts revealed development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of the grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellurized vascular graft to fabricate an RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with drug delivery function to prevent intimal hyperplasia. The RM-HTEV possessed superior mechanical properties over DRA and exhibited sustained drug release profile. In order to evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was operated on rats. Doppler-sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of the explanted grafts 12 weeks post-implantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV group, without impairing re-endothelialization and M2 macrophage polarization. Overall, RM-HTEV offers a promising strategy for developing small-diameter vascular grafts with great clinical translational potential.