Engineering of arteries in vitro

Abstract

This review will focus on two elements that are essential for functional arterial regeneration in vitro: the mechanical environment and the bioreactors used for tissue growth. The importance of the mechanical environment to embryological development, vascular functionality, and vascular graft regeneration will be discussed. Bioreactors generate mechanical stimuli to simulate biomechanical environment of arterial system. This system has been used to reconstruct arterial grafts with appropriate mechanical strength for implantation by controlling the chemical and mechanical environments in which the grafts are grown. Bioreactors are powerful tools to study the effect of mechanical stimuli on extracellular matrix architecture and mechanical properties of engineered vessels. Hence, biomimetic systems enable us to optimize chemo-biomechanical culture conditions to regenerate engineered vessels with physiological properties similar to those of native arteries. In addition, this article reviews various bioreactors designed especially to apply axial loading to engineered arteries. This review will also introduce and examine different approaches and techniques that have been used to engineer biologically based vascular grafts, including collagen-based grafts, fibrin-gel grafts, cell sheet engineering, biodegradable polymers, and decellularization of native vessels.

Fig. 1

Schematic diagrams of TEV ECM created from different non-mechanically conditioned methods. a Labels each ECM component of different TEVs. b The ECM of collagen gel-based TEVs with sparse de novo collagen fibers. c The ECM of fibrin gel-based TEVs, where cross-linked tropoelastin (elastin) can be seen. d The ECM of cell-sheet engineered TEVs. e The ECM of electrospun polymer scaffolds. f Degradable polymer scaffold seeded with cells on the day of implantation. g The ECM of decellularized arteries. h The ECM of native muscular arteries represented by undulated collagen fibers and mature elastic fibers as well as SMCs aligned in parallel with the collagen fibers

Fig. 2

Shows different vascular bioreactors that apply mechanical conditioning to generate TEVs. a Describes the Niklason pulsatile bioreactor in a schematic diagram. A peristaltic pump creates cyclic circumferential stretching by flowing PBS through the system. A silicone stopper is used to cap the bioreactor, and air filters allow gas exchange between the incubator and bioreactor. A pressure transducer measures and monitors the pressure at the upper stream of the flow system. ECM of the pulsed TEVs consists mainly of collagen fibers and SMCs as illustrated in a zoom in view. Small fragments of remaining PGA can still be seen in the ECM. b Schematic diagram of the Tranquillo bioreactor. The syringe is mounted on a reciprocating pump that causes the pulsed medium to flow transmurally through the tissue and axially through the lumens. TEVs in the front are shown to retract axially from the unfixed ends