Abstract：
Macrophages are the primary cell type orchestrating bioresorbable vascular graft (BVG) remodeling and infiltrate from three sources: the adjacent native vessel, circulating blood, and transmural migration from outer surface of the graft. To elucidate the kinetics of macrophage infiltration into the BVG, we fabricated two different bilayer arterial BVGs consisting of a macroporous sponge layer and a microporous electrospun (ES) layer. The Outer ES graft was designed to reduce transmural cell infiltration from the outer surface and the Inner ES graft was designed to reduce cell infiltration from the circulation. These BVGs were implanted in mice as infrarenal abdominal aorta grafts and extracted at 1, 4, and 8 weeks (n = 5, 10, and 10 per group, respectively) for evaluation. Cell migration into BVGs was higher in the Inner ES graft than in the Outer ES graft. For Inner ES grafts, the majority of macrophage largely expressed a pro-inflammatory M1 phenotype but gradually changed to tissue-remodeling M2 macrophages. In contrast, in Outer ES grafts macrophages primarily maintained an M1 phenotype. The luminal surface endothelialized faster in the Inner ES graft; however, the smooth muscle cell layer was thicker in the Outer ES graft. Collagen fibers were more abundant and matured faster in the Inner ES graft than that in the Outer ES graft. In conclusion, compared to macrophages infiltrating from the circulating blood, transmural macrophages from outside promote the acute inflammatory-mediated response for vascular remodeling and subsequent collagen deposition within BVGs. STATEMENT OF SIGNIFICANCE: To elucidate the kinetics of macrophage infiltration into the bioresorbable vascular graft (BVG), two different bilayer arterial BVGs were implanted in mice as infrarenal abdominal aorta grafts. Cell migration into BVGs was higher in the inner electrospun graft which cells mainly infiltrate from outer surface than in the outer electrospun graft which cells mainly infiltrate from the circulating blood. In the inner electrospun grafts, the majority of macrophages changed from the M1 phenotype to the M2 phenotype, however, outer electrospun grafts maintained the M1 phenotype. Collagen fibers matured faster in the Inner electrospun graft. Compared to macrophages infiltrating from the circulating blood, transmural macrophages from outside promote the acute inflammatory-mediated response for vascular remodeling and subsequent collagen deposition within BVGs.
摘要：
巨噬细胞是协调生物可吸收血管移植物（BVG）重塑和浸润的主要细胞类型，来自三个来源：相邻的天然血管，循环血液,和从移植物外表面的透壁迁移。为了阐明巨噬细胞渗入BVG的动力学，我们制造了两种不同的双层动脉BVG，由大孔海绵层和微孔电纺（ES）层组成。外ES移植物被设计成减少来自外表面的透壁细胞浸润,内ES移植物被设计成减少来自循环的细胞浸润。将这些BVGs作为肾下腹主动脉移植物植入小鼠中，并在第1、4和8周提取（每组n=5、10和10，分别)用于评估。在内部ES移植物中，细胞向BVG的迁移高于外部ES移植物。对于内部ES移植物，大多数巨噬细胞主要表达促炎M1表型,但逐渐转变为组织重塑M2巨噬细胞.相比之下,在外部ES移植物中，巨噬细胞主要维持M1表型。在内部ES移植物中，管腔表面内皮化更快；然而，外ES移植物的平滑肌细胞层较厚。与外部ES移植物相比，内部ES移植物中的胶原纤维更丰富且成熟更快。总之,与从循环血液中浸润的巨噬细胞相比，来自外部的透壁巨噬细胞促进急性炎症介导的血管重塑反应和随后的BVG内胶原沉积。重要声明：为了阐明巨噬细胞渗入生物可吸收血管移植物（BVG）的动力学，在小鼠中植入两种不同的双层动脉BVG作为肾下腹主动脉移植物。在细胞主要从外表面浸润的内部电纺移植物中，细胞向BVG的迁移高于细胞主要从循环血液浸润的外部电纺移植物。在内部电纺移植物中，大多数巨噬细胞从M1表型变为M2表型，然而,外电纺移植物保持M1表型。胶原纤维在内部电纺移植物中成熟更快。与从循环血液中浸润的巨噬细胞相比，来自外部的透壁巨噬细胞促进急性炎症介导的血管重塑反应和随后的BVG内胶原沉积。
