title: Appropriate density of PCL nano-fiber sheath promoted muscular remodeling of PGS/PCL grafts in arterial circulation.
abstract: Cell-free approach represents a philosophical shift from the prevailing focus on cells in vascular tissue engineering. Porous elastomeric grafts made of poly(glycerol sebacate) (PGS) enforced with polycaprolactone (PCL) nano-fibers degrade rapidly and yield neoarteries nearly free of foreign materials in rat abdominal aorta. However, considering the larger variation of blood pressure and slower host remodeling in human body than in rat, it is important to investigate the in vivo performance of PGS-PCL graft with enhanced mechanical properties, so that optimized arterial grafts could be developed for clinical translation. We acquired increasingly compacted sheath by prolonging the electrospinning period of PCL appropriately, which significantly enforced whole grafts. The rational design of sheath density significantly decreased the risk of dilation, rupture as well as enabling the long-term muscular remodeling. Since 3-12 months after implantation, the PGS grafts with rationally strengthened sheath were remodeled into neoarteries resembled native arteries in the following aspects: high patency rate and even vessel wall thickness; a confluent endothelium and contractile smooth muscle layers; expression of elastin, collagen and glycosaminoglycan; tough and compliant mechanical properties. Although loose sheath may result in rupture of vessel wall, adequate porosity was proved to be essential for sheath structure and directly determined muscular remodeling through M2 macrophage involved constructive remodeling. Therefore, this study confirmed that adequate density of PCL sheath in PGS grafts could initiate stable and high-quality muscular remodeling, which contributes to long-term success in arterial circulation before clinical translation.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Changle West Road 145, Xi'an, China; Department of Oral and Maxillofacial Surgery, Urumchi General Hospital of Lanzhou Military Region, Urumchi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Changle West Road 145, Xi'an, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Changle West Road 145, Xi'an, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Changle West Road 145, Xi'an, China. Electronic address: liuyanpu@fmmu.edu.cn.
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Changle West Road 145, Xi'an, China. Electronic address: wuweidds@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D001672:Biocompatible Materials / Q000737:chemistry*; D001807:Blood Vessel Prosthesis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D011091:Polyesters / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone
keywords: Electrospinning; Muscular remodeling; Poly(glycerol sebacate) (PGS); Sheath density; Vascular grafts; Vascular smooth muscle cells