Tropoelastin Inhibits Intimal Hyperplasia of Mouse Bioresorbable Arterial Vascular Grafts

Publication date: Available online 23 December 2016
Source:Acta Biomaterialia
Author(s): Tadahisa Sugiura, Riddhima Agarwal, Shuhei Tara, Tai Yi, Yong-Ung Lee, Christopher K. Breuer, Anthony S. Weiss, Toshiharu Shinoka
Neointimal hyperplasia, which results from the activation, proliferation and migration of vascular smooth muscle cells (SMCs), is a detrimental condition for vascular stents or vascular grafts that leads to stenosis. Preventing neointimal hyperplasia of vascular grafts is critically important for the success of arterial vascular grafts. We hypothesized that tropoelastin seeding onto the luminal surface of the graft would prevent neointimal hyperplasia through suppressing neointimal smooth muscle cell proliferation. In this study, we investigated the efficacy of tropoelastin seeding in preventing neointimal hyperplasia of bioresorbable arterial vascular grafts. Poly (glycolic acid) (PGA) fiber mesh coated with poly (l-lactic-co-ε-caprolactone) (PLCL) scaffolds reinforced by poly (l-lactic acid) (PLA) nano-fibers were prepared as bioresorbable arterial grafts. Tropoelastin was then seeded onto the luminal surface of the grafts. Tropoelastin significantly reduced the thickness of the intimal layer. This effect was mainly due to a substantial reduction the number of cells that stained positive for SMC (α-SMA) and PCNA in the vessel walls. Mature elastin and collagen type I and III were unchanged with tropoelastin treatment. This study demonstrates that tropoelastin seeding is beneficial in preventing SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts.Statement of SignificanceSmall resorbable vascular grafts can block due to the over-proliferation of smooth muscle cells in neointimal hyperplasia. We show here that this the proliferation of these cells is restricted in this type of graft.This is achieved with a simple dip, non-covalent coating of tropoelastin. This is in principle amendable to other grafts and is therefore an attractive process.This study is particularly significant because: (1) it shows that smooth muscle cell proliferation can be reduced while still accommodating the growth of endothelial cells, (2) small vascular grafts with an internal diameter of less than 1 mm are amenable to this process, and (3) this process works for resorbable grafts.

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