Endothelial Cell-Mediated Gene Delivery for In Situ Accelerated Endothelialization of a Vascular Graft

Abstract

As an urgently needed device for vascular diseases, the small-diameter vascular graft is limited by high thrombogenicity in clinical applications. Rapid endothelialization is a promising approach to construct an antithrombogenic inner surface of the vascular graft. The main bottleneck for rapid endothelialization is the adhesion, migration, and proliferation of endothelial cells (ECs) in situ of the small-diameter vascular graft. Herein, we innovatively fabricated an intelligent gene delivery small-caliber vascular graft based on electrospun poly­(lactic acid-co-caprolactone) and gelatin for rapid in situ endothelialization. The graft surface was co-modified with EC adhesive peptide of Arg-Glu-Asp-Val (REDV) and responsive gene delivery system. REDV can selectively adhere ECs onto the graft surface; subsequently, the overexpressed matrix metalloproteinase by ECs can effectively cleave the linker peptide GPQGIWGQ-C; and finally, the gene complexes were intelligently and enzymatically released from the graft surface, and thereby, the gene can efficiently transfect ECs. Importantly, this enzymatically releasing gene surface has been proven to be safe and temporarily stable in blood flow owing to the biotin–avidin interaction to immobilize gene complexes on the inner surface of vascular grafts through the GPQGIWGQ-C peptide linker. It has the advantage of specifically adhering the ECs to the surface and smartly transfecting them with high transfection efficiency. The co-modified surface has been demonstrated to accelerate the luminal endothelialization in vivo, which might be attributed to the synergistic effect of REDV and effective gene transfection. Particularly, the intelligent and responsive gene release surface will open a new avenue to enhance the endothelialization of blood-contacting devices.

Biodegradable cross‐linked poly(1,3‐trimethylene carbonate) networks formed by gamma irradiation under vacuum

“…The degradation of PTMC can be accelerated in the presence of enzymes. The same phenomenon was reported in previous articles for non‐cross‐linked PTMC 7 . Meanwhile, according to our previous study, the mass loss of non‐cross‐linked PTMC in enzyme solution was 5.3% ± 0.4%.…”

“…Compared with metal materials and nondegradable polymer materials, biodegradable polymers have the advantage of not requiring secondary surgery 3 . In recent decades, polylactic acid, 4 polycaprolactone, 5 polyglycolic acid, 6 and other absorbable polymer materials are increasingly favored by researchers 7,8 …”

Recent advances in inhibiting atherosclerosis and restenosis: from pathogenic factors, therapeutic molecules to nano-delivery strategies

“…(B) REDV peptide and MMP cleavable peptide comodified surface to programmatically attract VECs and release ZNF580 gene complexes. 209 Copyright 2021, American Chemical Society.…”

“…5B). 209 The comodified surface could selectively adhere ECs firstly, and subsequently release gene nanocomplexes to transfect ECs, which synergistically accelerates re-endothelialization. Recently, Cheng's group constructed smart exosome-eluting scaffolds by using ROS responsive groups to link metal scaffolds to phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and then attaching exosomes uniformly to metal scaffolds.…”

Impact of Tether Length and Flexibility on the Efficiency of Analyte Capture by Tethered Receptors

“…NAv/biotin complex is the strongest non-covalent interaction known in nature (Kd = 10 -14 mol/L) and has been used in a wide variety of applications including: bioassays, [43] drug delivery [44] and tissue engineering. [45] As such, neutravidin (and the streptavidin companion) are used in immunosensing applications because of their reduced nonspecific binding. [46] It has been demonstrated that passive surface adsorption of Neutravidin leads to protein alteration in terms of conformation and aggregation (multilayers) which may alter the interface outcome, and that can be overcome by the use of PEG tethers.…”