The effect of Substance P/Heparin conjugated PLCL polymer coating of bioinert ePTFE vascular grafts on the recruitment of both ECs and SMCs for accelerated regeneration

Donghak Kim,Youngmee Jung,Soo Hyun Kim,Justin J Chung

doi:10.1038/s41598-019-53514-6

Abstract

Artificial vascular grafts consisting of ePTFE have been mainly used in clinics for the treatment of cardiovascular disease. However, artificial grafts can become clogged after a long time due to thrombosis, as graft maturation by endothelialization is limited. The strategy introduced in this study is to induce graft remodeling through interaction between the bioinert graft and the body. The Substance P (SP) and heparin were covalently conjugated with PLCL, an elastic biocompatible copolymer and the Substance P-conjugated PLCL (SP-PLCL) and/or heparin-conjugated PLCL (Hep-PLCL) were vacuum-coated onto ePTFE vascular grafts. To assess the effectiveness of the coating, coated samples were evaluated by implanting them subcutaneously into SD-Rats. Coatings allow grafts to be remodeled by creating a microenvironment where cells can grow by infiltrating into the grafts while also greatly enhancing angiogenesis. In particular, a double coating of Hep-PLCL and SP-PLCL (Hep/SP-PLCL) at four weeks showed markedly improved vascular remodeling through the recruitment of mesenchymal stem cells (MSCs), vascular cells (ECs, SMCs) and M2 macrophages. Based on these results, it is expected that when the Hep/SP-PLCL-coated ePTFE vascular grafts are implanted in situ, long-term patency will be assured due to the appropriate formation of an endothelial layer and smooth muscle cells in the grafts like native vessels.

Highlights

Vascular diseases continue to threaten human life
The FT-IR spectra identified a new peak that does not exist in relation to the PLCL emergence at 3407 cm−1 in Substance P (SP)-PLCL, indicating that the primary amine (N-H stretching vibrations) of SP immobilized onto the terminal hydroxyl groups of the long PLCL polymer chain
As determined by the X-ray photoelectron spectroscopy (XPS) analysis, the intensity of the N1s peak increased in Substance P-conjugated PLCL (SP-PLCL) compared to that in the PLCL, indicating that the nitrogen of SP conjugated to PLCL, which does not exist in PLCL

Summary

Introduction

Vascular diseases continue to threaten human life. As a clinical treatment method, the transplantation of vascular autografts has served as an effective strategy. Through a polymer coating, we intended to remodel ePTFE artificial vascular grafts by recruiting SMCs and ECs with bioactive molecules capable of instructing the surrounding tissues to migrate into the graft, stimulating the recruitment and differentiation of stem cells, inducing angiogenesis, and promoting regeneration. Heparin is a component of the extracellular matrix of blood vessels and promotes endothelial cell growth in vitro[24] It demonstrates numerous important biological activities associated with its interaction with diverse proteins, including enzymes, lipoproteins, viral coat proteins, and extracellular matrix proteins, especially cytokines and growth factors due to the specific electrostatic interactions between the negatively charged sulfate groups of heparin and the positively charged amino acid residues of proteins[20,25,26,27,28,29]. We have previously implanted samples into the subcutaneous tissue and tested the possibility

Methods

Results

Discussion

Conclusion