A Brief Report on an Implantation of Small-Caliber Biodegradable Vascular Grafts in a Carotid Artery of the Sheep

Abstract

The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. The 4 mm diameter vascular grafts were manufactured using a mix of polyhydroxybutyrate/valerate and polycaprolactone supplemented with growth factors VEGF, bFGF and SDF-1α (PHBV/PCL-GFmix) and additionally modified by a polymer hydrogel coating with incorporation of drugs heparin and iloprost (PHBV/PCL-GFmixHep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity.

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

“…Future implantation using scaffolds larger than 5 cm are needed. (PHBV/PCL-GFmix) performed well when implanted in the rat abdominal aortas [29]. Subsequently, they used a sheep model, which is considered to be more suitable for the in vivo testing of cardiovascular implants [39].…”

“…Electrospinning technology is often used to create grafts that take into account a variety of important properties of bioabsorbable synthetic grafts, such as degradation rate, [29]. Subsequently, they used a sheep model, which is considered to be more suitable for the in vivo testing of cardiovascular implants [39].…”

“…(C) Long release profile. Adopted with permission from Shinoka et alAntonova et al have shown that polyhydroxybutyrate/valerate(PHBV)/polycaprolactone (PCL) grafts modified with growth factors such as VEGF, bFGF, and SDF-1α (PHBV/ PCL-GFmix) performed well when implanted in the rat abdominal aortas[29]. Subsequently, they used a sheep model, which is considered to be more suitable for the in vivo testing of cardiovascular implants[39].…”

Composite P(3HB-3HV)-CS Spheres for Enhanced Antibiotic Efficiency

“…Some intrinsic characteristics of P(3HB-3HV), such as stiffness/flexibility and tensile strength, melting point and glass transition temperature, depend on the ratio between constituent monomers [ 16 , 17 ]. Other features, like porosity, wettability, water and oxygen permeability and biological effects, can be improved though the development of P(3HB-3HV)-based composites [ 28 , 29 , 30 ].…”

Comparative Analysis of the Hemostasiological Profile in Sheep and Patients with Cardiovascular Pathology as the Basis for Predicting Thrombotic Risks During Preclinical Tests of Vascular Prostheses

“…Notably, some of them (for example, sheep model) are the most aggressive in terms of identifying hemostasiological risks associated with failure of tested vascular prostheses. In most cases, using this model makes it possible to achieve implanted prostheses patency of a little more than 60% [ 4 , 5 ]. To date, the causes of aggressive response of hemostatic system of sheep during preclinical tests of vascular prostheses are still understudied.…”