Development of a decellularized human amniotic membrane-based electrospun vascular graft capable of rapid remodeling for small-diameter vascular applications

Abstract

The performance of small-diameter vascular grafts adapted to vascular replacement is commonly hindered by stenosis. To address this issue, a graft featuring rapid remodeling with degradation is warranted. In this work, a 1.8-mm-diameter graft was constructed by fabricating a decellularized human amniotic membrane (HAM) with polycaprolactone (PCL)/silk fibroin (SF) around it through electrospinning, namely, an HPS graft, and applied in a rat aortic grafting model for comparison to a decellularized porcine small intestinal submucosa (SIS)-integrated PCL/SF (SPS) graft and an autologous aorta. In vitro studies demonstrated that HAM provided a bioactive milieu for rapid endothelial cell proliferation and resisting fibroblast-induced collagen secretion. PCL/SF provides a biocompatible microenvironment for cellular infiltration with mechanical properties resembling those of the rat aorta. In vivo studies showed that the HPS graft induced functional endothelialization more rapidly, along with less intensive ECM deposition than the SPS graft upon the histologically weaker inflammatory response and foreign body reaction 4 weeks after implantation, and maintained patency by progressively stabilizing the remodeling structure approximating the native counterparts over 24 weeks. The bioengineered graft expands the applicability of allogeneic matrices with degradable electrospun polymers for long-term in situ vascular applications. STATEMENT OF SIGNIFICANCE: An orchestrated remodeling of the vascular graft, featuring rapid endothelialization and resisting extracellular matrix (ECM) deposition on the luminal surface, with a mechanically stable structure, is requisite for long-term vascular patency. Nevertheless, off-the-shelf grafts might not fulfil the criteria under abdominal aortic pressure. Herein, we fabricated a 1.8-mm-diameter vascular graft through the integration of a decellularized human amniotic membrane (HAM) with electrospun polycaprolactone (PCL)/silk fibroin (SF). In a rat aortic grafting model, the graft is capable of rapid endothelialization and resisting collagen deposition and provides a native-like mechanical structure for stabilizing the remodeling process towards that of the native aorta. This bioengineered graft has potential for small-diameter vascular regeneration, and provides advanced strategies to facilitate full-remodeling tissue applications.

Keywords: Bioengineered vascular graft; Electrospinning; Endothelialization; Human amniotic membrane; Remodeling.