Bioinspired, Artificial, Small-Diameter Vascular Grafts with Selective and Rapid Endothelialization Based on an Amniotic Membrane-Derived Hydrogel

Clinical application of the amniotic membrane (AM) in vascular reconstruction was limited by poor processability, rapid biodegradation, and insufficient hemocompatibility. In this work, decellularized AM was digested to a thermosensitive hydrogel and densely cross-linked in the nanoscale as “enhanced” collagenous fibers. Via N-(3-dimehylaminopropyl)-N′-ethylcarbodiimide and N-hydroxysuccinimide (EDC/NHS) catalysis, REDV was further grafted to simulate anticoagulant substances on naturally derived blood vessels. This modification approach endowed AM with rapid endothelialization and rare vascular restenosis. Through adjusting the fixation condition, the pore size and mechanical stability of the fiber network were approximate to those of natural tissues and precisely designed to fit for cell adhesion. AM was synchronously fixed by alginate dialdehyde (ADA) and EDC/NHS, forming a “double-cross-linked” stable structure with significantly improved mechanical strength and resistance against enzymic degradation. The hemolytic and platelet adhesion test indicated that ADA/REDV-AM could inhibit hemolysis and coagulation. It also exhibited excellent cytocompatibility. It selectively accelerated adsorption and migration of endothelial cells (ECs) while impeding adhesion and proliferation of smooth muscle cells (SMCs). It maintained EC superiority in competitive growth and avoided thrombosis in vivo. Furthermore, its property of promoting reconstruction and repair of blood vessels was proved in an animal experiment. Overall, the present study demonstrates that ADA/REDV-AM has potential application as a small-diameter artificial vascular intima with rapid endothelialization and reduced SMC/platelet adhesion.