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

Abstract

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.

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“…The C-terminal and N-terminal closure of REDV peptide does not affect the role of REDV, so REDV has a variety of derivatives. 121 Thiol-ene click reaction 122 EDC/ NHS cross-linking 123 2. In order to achieve better endothelialization in vivo, the combination of REDV peptides with other biological factors is also essential.…”

A Review on Modifications of Amniotic Membrane for Biomedical Applications

“…Moreover, while it inhibited platelet activation and hemolysis, this graft enhanced the adhesion and expansion of endothelial cells as well as vascular remodeling and repair. In a similar experiment, Peng et al (2020) used D-double-cross-linked decellularized AM hydrogel grafted with REDV(ArgGlu-Asp-Val) polypeptides which showed excellent mechanical strength and resistance to enzymatic degradation and inhibited hemolysis and coagulation (similar characteristics to the vascular graft developed by Lei et al). Also, the addition of REDV to this structure stimulated natural anticoagulant substances on naturally derived blood vessels.…”

Tissue Engineering for Mimics and Modulations of Immune Functions

“…DOPA‐pCB was the most effective, with fibrin and gross thrombus formation decreasing by 59% and applicable to multiple surface materials. Other biomolecules such as polyelectrolytes, [ 48 ] ACH 11 antithrombotic peptide, [ 49 ] reactive oxygen species (ROS)‐responsive antithrombogenic drug, [ 41 ] and Arg‐Glu‐Asp‐Val (REDV) peptide, [ 50 ] were also embedded or grafted to vascular grafts for anticoagulation. Dextran sulfate was self‐assembled onto an electrospun chitosan/PCL scaffold.…”

“…grafted the REDV peptide, which inhibits nonspecific adhesion of platelets, to decellularized amniotic membrane (AM) hydrogel through EDC/NHS coupling. [ 50 ] Moreover, it has been reported that physical properties such as fiber diameter also affect anticoagulation properties. For example, Yu et al.…”