The Tissue-Engineered Vascular Graft-Past, Present, and Future

Abstract

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented.

FIG. 1.

Patency rates for small-diameter vascular bypass procedures using the saphenous vein (SV) and polytetrafluoroethylene (PTFE) conduits (data for coronary artery bypass grafting [CABG] using PTFE conduits were only available up to 45 months).^,,,,

FIG. 2.

Scaffold-based tissue-engineered vascular graft (TEVG) manufacture. Cells are harvested from the patient and the required types isolated and expanded in vitro. The cells are then mixed with a scaffold-forming material, such as collagen or fibrin, and shaped in a tubular mold or seeded onto a porous polymer scaffold. The construct is then cultured in a bioreactor and may be conditioned to develop suitable mechanical properties for use as a TEVG. Color images available online at www.liebertpub.com/teb

FIG. 3.

TEVG manufacture using decellularized matrices. Tissue is harvested from an animal source and decellularized using various chemical and/or mechanical processes. Where vascular tissue is decellularized, the result is a tube comprising only extracellular matrix (ECM). Decellularized nonvascular tissue, such as small intestinal submucosa (SIS) or amniotic membrane, may be shaped into a tubular construct. Cells extracted from the patient are then seeded onto the decellularized scaffold forming a TEVG after maturation. Color images available online at www.liebertpub.com/teb

FIG. 4.

TEVG manufacture by self-assembly. (a) Sheet-based tissue engineering—a 2D cell sheet is cultured and then shaped around a mandrel, forming a tube that is matured into a TEVG; (b) Assembly of microtissues—cell aggregates placed in a mold and combined to form a TEVG; (c) Bioprinting—cells and supporting material are deposited in a layer-by-layer manner, building up a 3D construct. Color images available online at www.liebertpub.com/teb

FIG. 5.

The mechanical properties of reported TEVGs compared with the human internal thoracic artery (ITA) and SV. The results are arranged by manufacturing method and represent grafts before any implantation. For reference, values for burst pressure, suture retention strength, and compliance are 3073 mmHg, 1.72 N, and 11.5%/100 mmHg for the ITA and 2134 mmHg, 1.92 N, and 25.6%/100 mmHg for the SV, respectively.^, Color images available online at www.liebertpub.com/teb

FIG. 6.

Representative stress–strain responses for the ITA and SV. Both vessels exhibit a J-shaped stress-strain response with a linear toe region. Color images available online at www.liebertpub.com/teb

FIG. 7.

Pathway for the development of the TEVG from design concept to clinical success and then clinical adoption. The various criteria for achieving these milestones are detailed and discussed in relation to the three major TEVG design methodologies. Color images available online at www.liebertpub.com/teb