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Small-diameter synthetic vascular grafts do not recapitulate native blood vessel’s structural heterogeneity, which in the case of arteries, is based on the morphologically distinct tunica intima, media, and adventitia. These layers differ in composition and as a result in their specific function [1].
It can be then speculated that when one of these structures is neglected in the design of a device for coronary artery bypass, arteriovenous fistulae, or dialysis access a corresponding function will be impaired. For example, intima hyperplasia is one of the most common mechanisms of failure in commercially available vascular grafts, and it can be attributed to the absence of a tunica intima or to the absence of an adequate artificial structure within the graft able to fulfill an equivalent function [2].
The excessive proliferation of smooth-muscle-cells (SMCs) in artificial graft generally leads to a decrease in lumen patency, vessels obstruction, and thrombus formation. Multiple other factors can aggravate this process such as a mechanical compliance mismatch between the native tissue, and the graft as well as altered hemodynamic conditions that are in turn dictated by non-physiological wall shear stress.
This study proposes a three-layered bio-inspired scaffold designed to prevent hyperplasia by introducing the notion of structural and bioactivity gradients in tissue engineering small-diameter vascular graft (TEVG).
Biomimicry of morphological characteristics of the tissue, such as inner wall thicknesses, inner diameter, outer diameter, was based on scanning electron microscopy (SEM) of explanted porcine coronary arteries (N=3).
Next, two bio-processing techniques were utilized to create three morphologically different layers: thermally induced phase separation (TIPS), and electrospinning (ES). The tunica media was reproduced as a bioactive layer composed of decellularized small intestinal submucosa ExtraCellular Matrix gel (ECM) seeded with rat SMCs. While the adventitia and intima layers were produced by using poly(ester urethane)urea proceeded by TIPS and ES due to its biocompatible and biodegradable properties.
Four different configurations were fabricated for TEVG scaffolds where the three layers combination were permutated as follow: ES-ECM-TIPS; ES-ECM-ES; TIPS-ECM-TIPS; TIPS-ECM-ES. Each TEVG was tested under dynamic conditions using a pulsatile custom-made bioreactor. Histological analysis was conducted to quantify SMCs distribution per layer (cells/unit area) and cell migration (7 days).
After 7 days of dynamic culture, preliminary histological analysis confirmed the hypothesis that the cell-seeded in the central portion of the graft migrated towards the most porous graft layer (TIPS) suggesting that a structural and bioactive gradient can mitigate the intima overgrowth.
In the three-layer TEVG, with the TIPS-ECM-ES configuration, showed that the electrospun fibrous structure can act as a barrier [3] limiting cell infiltration into the intima. This in conjunction with a more penetrable layer (TIPS) can lead to tailored cell migration.
- Holzapfel, G.A., Am. J. Physiol.- Heart Circ. Physiol., 289, 2048-2058 (2005).
- Seifu, D.G., Nat Rev Cardiol., 10, 410-421 (2013).
- D'Amore, A., Tissue Eng. Part A, 24, 889-904 (2018).
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