Experiment Research On PGS/PCL Bi-layered Vascular Grafts Inducing And Remodeling Carotid Artery In Vivo

Head and neck tumor constitute 6% of all human malignancies and always invand the carotid artery resulting in extremely poor prognosis. Carotid resection with the tumor and reconstruction can be a curative treatment option. However, it requires an ideal vascular graft to replace the invanded carotid artery by malignancies. Similarly, Cardiovascular disease remains the major cause of mortality among adults in the worldwide. And in most instances of long-term maintenance hemodialysis, a permanent arteriovenous access is required, and so on. In clinical, many effective treatments for related diseases urgently require an ideal varscular grafts, which can perform functions as healthy blood vessel, and don’t cause related complications. However, from the introduction of the triangulated vascular anastomosis and subsequent development of the field of transplantation by Alexis Carrel, researchers in the worldwide persisted continuously to design an ideal TEVG. Nevertheless, so far, except autologous vessels, the most common type of material used to vascular transplantation is biocompatible synthetic polymers, such as Dacron or Gore-Tex. These non-biodegradable materials as a foreign body existing in the human body are associated with numerous short- and long-term complications, which drive people continuously to research an ideal design for TEVG. Although, some TEVGs have been researched in human body and achieve some degree success,it is only in phrase of clinical trail for many other disadvantages.Based on the former researchers and our personal practical experiences, we have fabricated PGS-PCL bi-layered vascular grafts with opening porous inner part and electrospun PCL nanofibers wrapped outside. In vivo results showed PGS-PCL grafts is fast degradable, which fully harnessed the host remodeling capacity to regenerate artery. PCL nano-fiber sheath outside PGS endowed scaffold with adequate mechanical support such as suture retention, pressure resistance and blood sealing. Rapid cell recruitment and production of ECM compensate the degradation of PGS scaffold and vitalized the grafts. By three-month post-implant, grafts transformed into tissues grossly resembling native aortas with similar tissue architecture and no visible graft material residues However, we found PGS-PCL grafts always regenerate vessel wall with uneven thickness at the early stage, which may cause aneurysmal dilatation or graft rupture in the context of clinical application of arterial grafts, as is the most catastrophic risks of graft implantation. Moreover, we found less muscular remodeling in some grafts implanted for 1 year, which may cause stiffening of vessel wall, weakening function and probably long-term failure. Owing to the rapid degradation of PGS itself, PCL sheath is the only factor which could influence the midlater term remodeling. It is important to continue to investigate the temporal changes of PGS-PCL graft with variant sheath microstructure, so that further optimized arterial grafts could be developed for clinical translation.In order to evaluate the influence of sheath structure in graft mediated host remodeling and offer rational design of sheath parameter, in this study, we fabricated three different type of PGS-PCL vascular grafts with diffferrent and representive sheath microstructure by extending the electrostatic spinning time. Increasing amount of PCL nano-fibers could provide PGS grafts with significantly enforced strength, thus increased clinical safety. We further evaluated cell infiltration and alignment in the scaffolds and assessed the muscular remodeling in vivo by implanting bi-layered grafts into rat abdominal aorta, so that the rational design of PCL sheath could be acquired for clinical translation. Additionally, for investgating the advantage in carotid artery regeneration, we implanted optimized PGS/PCLgraft in rat carotid artery and choosed implanted external jugular acted as controls.In present study, we found increasing density of PCL nano-fibers significantly improved mechanical strength of PGS-PCL grafts. More interestingly, the modification of sheath density significantly changed long-term muscular remodeling of PGS-PCL grafts. Adequate density in PCL sheath significantl improved the long-term behavior of regenerated artery, which presented as stable differentiation of recruited SMCs, stable and smooth vessel remodeling. Furthermore, the adventitia angiogenesis and M2 macrophage infiltration are closely related to sheath density and microstructure, which is regarded to regulate muscular remodeling and tissue phenotypes. These findings confirmed that rational design of PCL sheath around PGS grafts could initiate highquality muscular remodeling, which contributes to adequate pressure resistance, ideal surgical handling, as well as long-term success in arterial circulation before clinical translation. The study of carotid reconstruction demonstrates that a fast-resorbing, cell-free vascular graft can remodel in situ into neoartery with good stability and likeness to healthy carotid arteries. The neoartery has more advantage than implanted external jugular, such as: no calcification, no hyperplasia in vessel wall, a large number elastin depositing in the vessel wall, loose adventitia and nerve regeneration in vessel wall. These results suggest that this design may well achieve the regeneration of muscle carotid artery with well contractility and flexibility, and provide a new repair method for treatment of head and neck tumor involving resection of the carotid artery.