Small Diameter Cell-Free Tissue-Engineered Vascular Grafts: Biomaterials and Manufacture Techniques to Reach Suitable Mechanical Properties

Abstract

Vascular grafts (VGs) are medical devices intended to replace the function of a blood vessel. Available VGs in the market present low patency rates for small diameter applications setting the VG failure. This event arises from the inadequate response of the cells interacting with the biomaterial in the context of operative conditions generating chronic inflammation and a lack of regenerative signals where stenosis or aneurysms can occur. Tissue Engineered Vascular grafts (TEVGs) aim to induce the regeneration of the native vessel to overcome these limitations. Besides the biochemical stimuli, the biomaterial and the particular micro and macrostructure of the graft will determine the specific behavior under pulsatile pressure. The TEVG must support blood flow withstanding the exerted pressure, allowing the proper compliance required for the biomechanical stimulation needed for regeneration. Although the international standards outline the specific requirements to evaluate vascular grafts, the challenge remains in choosing the proper biomaterial and manufacturing TEVGs with good quality features to perform satisfactorily. In this review, we aim to recognize the best strategies to reach suitable mechanical properties in cell-free TEVGs according to the reported success of different approaches in clinical trials and pre-clinical trials.

Patient-specific tissue engineered vascular graft for aortic arch reconstruction

“…Previous studies have reported limited cellular infiltration and integration of PCL/PLCL grafts implanted in arteries, with high rates of thrombosis and neointimal hyperplasia. 20 , 21 Intimal thickening and subsequent vascular remodeling over time can lead to stenosis and occlusion, which are associated with various health risks such as hypertension, myocardial infarction, and stroke. 22 However, this study showed that large-diameter grafts may not cause graft stenosis compared with small-diameter grafts, although there may be some intimal thickening.…”

Integrated biophysical matching of bacterial nanocellulose coronary artery bypass grafts towards bioinspired artery typical functions

“…Our motivation on BNC-CAGB prosthesis optimization by integrated approaches on guiding endothelial alignment and flow patterns could be successfully realized by using the MMR-Tech technology and thereby effecting the BNC density via the bacterial working cell density on the one hand and via vectored luminal micro topographies on the other hand. Doing so, at first, we addressed the long-lasting and widely investigated roadblock of biomechanical mismatching in between synthetic vascular grafts and the host 5 , 17 , 18 . In contrast to the MMR-Tech derived BNC-CAGB prosthesis that we used in earlier studies 26 – 28 , 45 , we could increase c X_w by two orders of magnitude and advance the biomechanical properties towards artery typical stress-strain relations.…”

“…Interestingly, though widely approached, the problem of mechanical mismatching for vascular grafts continues even to advanced approaches that made it to pre-clinical models. To estimate the potential clinical performance, these recently got contrasted to GSV 17 . One step beyond, a very recent study on BNC-CABG grafts used a surgical mesh to reinforce the mechanical properties and showed decreased luminal narrowing in vivo 48 .…”

“…As the vascular biophysicalniche can be defined by reciprocally involved contact and flow derived stresses, like topography and shear stress, curvature and pressure or stiffness and wall strain 16 , tailoring biomimetic stimulation stresses can be realized by controlling mainly (i) elasticity and (ii) form &topography. On this matter, currently the generation of functional synthetic CAGB grafts still is blocked mainly by the unsolved challenge inmatching the biomechanical properties between CABG and the host in (i) and suffers from corresponding disturbances in flow and mechanotransduction 5 , 17 , 18 .…”

Dragging 3D printing technique controls pore sizes of tissue engineered blood vessels to induce spontaneous cellular assembly

“…Accordingly, artificial blood vessel grafts to replace autologous blood vessels are being manufactured in the field of tissue engineering [ [9] , [10] , [11] , [12] ]. Due to the high clinical demand for artificial blood vessel grafts, several off-the-shelf products have been developed using synthetic polymers (e.g., polyethylene terephthalate (Dacron) and polytetrafluoroethylene (Teflon) and ePTFE (GORE-TEX)) [ [13] , [14] , [15] , [16] ]. These artificial blood vessel grafts have been able to successfully replace diseased vessels when transplanting medium or large diameter blood vessels [ [15] , [16] , [17] ].…”