In Vivo Evaluation of Gamma-Irradiated and Heparin-Immobilized Small-Diameter Polycaprolactone Vascular Grafts with VEGF in Aged Rats

Abstract

The effectiveness of small-diameter vascular grafts depends on their antithrombogenic properties and ability to undergo accelerated endothelialization. The extreme hydrophobic nature of poly(ε-caprolactone) (PCL) hinders vascular tissue integration, limiting its use in medical implants. To enhance the antithrombogenicity of PCL as a biomaterial, we grafted 2-aminoethyl methacrylate (AEMA) hydrochloride onto the PCL surface using gamma irradiation; developed a biodegradable heparin-immobilized PCL nanofibrous scaffold using gamma irradiation and N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride/N-hydroxysuccinimide reaction chemistry; and incorporated vascular endothelial growth factor (VEGF) into the scaffold to promote vascular endothelial cell proliferation and prevent thrombosis on the vascular grafts. We assessed the physicochemical properties of PCL, heparin-AEMA-PCL (H-PCL), and VEGF-loaded heparin-AEMA-PCL (VH-PCL) vascular grafts using scanning electron microscopy, attenuated total reflection–Fourier transform infrared spectroscopy, toluidine blue O staining, and fibrinogen adsorption and surface wettability measurement. In addition, we implanted the vascular grafts into 24-month-old Sprague Dawley rats and evaluated them for 3 months. The H-PCL and VH-PCL vascular grafts improved the recovery of blood vessel function by promoting the proliferation of endothelial cells and preventing thrombosis in clinical and histological evaluation, indicating their potential to serve as functional vascular grafts in vascular tissue engineering.

Recent Developments and Current Challenges of Heparin-Grafted Hemodialysis Membranes

“…Heparin was also used to improve the hemocompatibility and hydrophilicity of the extreme hydrophobic nature of poly(ε-caprolactone) (PCL) to create vascular graft implants [60]. Heparin-coated PCL nanofibrous scaffolds were prepared using gamma irradiation and N-(3-dimethylaminopropyl)-N -ethyl carbodiimide hydrochloride/N-hydroxysuccinimide reaction chemistry on a preliminary 2-aminoethyl methacrylate (AEMA) hydrochloride grafted surface.…”

In Vivo Evaluation of PCL Vascular Grafts Implanted in Rat Abdominal Aorta

“…However, both the polymer itself and its degradation products are non-toxic and nonimmunogenic [2,4,[10][11][12]. In this regard, many authors have tried to improve the properties of electrospun PCL matrices by introducing different additives and combining them with other natural and synthetic polymers [2,4,5,[12][13][14][15].…”