Small Caliber Compliant Vascular Grafts Based on Elastin-Like Recombinamers for in situ Tissue Engineering.

Alicia Fernández-Colino,Stefan Jockenhoevel,Jose Carlos Rodríguez-Cabello,Thomas Schmitz-Rode,Stephan Rütten,Petra Mela,Frederic Wolf

doi:10.3389/fbioe.2019.00340

Abstract

Vascular disease is a leading cause of death worldwide, but surgical options are restricted by the limited availability of autologous vessels, and the suboptimal performance of prosthetic vascular grafts. This is especially evident for coronary artery by-pass grafts, whose small caliber is associated with a high occlusion propensity. Despite the potential of tissue-engineered grafts, compliance mismatch, dilatation, thrombus formation, and the lack of functional elastin are still major limitations leading to graft failure. This calls for advanced materials and fabrication schemes to achieve improved control on the grafts' properties and performance. Here, bioinspired materials and technical textile components are combined to create biohybrid cell-free implants for endogenous tissue regeneration. Clickable elastin-like recombinamers are processed to form an open macroporous 3D architecture to favor cell ingrowth, while being endowed with the non-thrombogenicity and the elastic behavior of the native elastin. The textile components (i.e., warp-knitted and electrospun meshes) are designed to confer suture retention, long-term structural stability, burst strength, and compliance. Notably, by controlling the electrospun layer's thickness, the compliance can be modulated over a wide range of values encompassing those of native vessels. The grafts support cell ingrowth, extracellular matrix deposition and endothelium development in vitro. Overall, the fabrication strategy results in promising off-the-shelf hemocompatible vascular implants for in situ tissue engineering by addressing the known limitations of bioartificial vessel substitutes.

Highlights

Cardiovascular disease is the most common cause of death worldwide (Townsend et al, 2016)
The concept of ready-to-use vascular grafts implies the absence of any in vitro seeding of the device prior implantation. Such device will be in direct contact with blood before a native endothelium covers its surface, and the first requirement that the base material has to meet is to be hemocompatible
We first evaluated the hemocompatibility of the elastin-like recombinamers (ELRs) by assessing the activation of the complement system

Summary

Introduction

Cardiovascular disease is the most common cause of death worldwide (Townsend et al, 2016). The progressive constriction and stiffening of the blood vessels requires, in complex conditions, bypass surgery (Townsend et al, 2016). Native autologous vein and artery segments remain the gold standard as grafts for this procedure, but they are not always available due to a previous harvest, anatomical variability or disease progression. The failure rate of saphenous vein grafts, the most widely used conduits for coronary artery bypass, reaches 25% during the first 12–18 months after surgery, clearly showing the need for better solutions (Hess et al, 2014). The synthetic vascular prostheses available today are made of expanded polytetrafluoroethylene (GORE-TEX R ), poly(ethylene terephthalate) (Dacron) or polyurethane. These vascular prostheses lack the remodeling and growing capabilities of living tissues and are not suitable as small-diameter substitutes (

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Conclusion