Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise

Abstract

Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological function. Here we explore recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source. We also highlight progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications of this technology.

Figure 1. Fabrication Approaches for Engineering Arterial Vessels

Tubular structures that resemble arteries (<6mm in diameter) can be xenogenically sourced or fabricated with biomaterials through sheet rolling, molding, and/or direct scaffolding. Once fabricated, the grafts are seeded with ECs and SMCs and conditioned with biomechanical stimuli (not shown) before implantation. Grafts can also be used without cellularization for applications such as hemodialysis access.

Figure 2. Fabrication Approaches for Engineering Microvessels

Microvessels can be fabricated using either A) top-down or B) bottom-up methods. A) Top-down approaches involve fabrication of pre-designed structures through i) sacrificial 3D printing, ii) spatial laser-degradation, or iii) layer-by-layer assembly (z-axis illustrated normal to figure plane). B) Bottom-up approaches utilize chemical/physical stimulants to induce i) angiogenic sprouting or ii) vasculogenic self-assembly of endothelial cells (ECs) to create a network of interconnected microvessels. Dimensions of fabricated structures can vary but all are sub-millimeter in scale.