An intelligent bioreactor system for the cultivation of a bioartificial vascular graft

Abstract

Cardiovascular disease is the most common cause of death, accounting for 31% of deaths worldwide. As purely synthetic grafts implicate concomitant anticoagulation and autologous veins are rare, tissue‐engineered vascular grafts are urgently needed. For successful in vitro cultivation of a bioartificial vascular graft, the suitable bioreactor should provide conditions comparable to vasculogenesis in the body. Such a system has been developed and characterized under continuous and pulsatile flow, and a variety of sensors has been integrated into the bioreactor to control parameters such as temperature, pressure up to 500 mbar, glucose up to 4.5 g/L, lactate, oxygen up to 150 mbar, and flow rate. Wireless data transfer (using the ZigBee specification based on the IEEE 802.15.4 standard) and multiple corresponding sensor signal processing platforms have been implemented as well. Ultrasound is used for touchless monitoring of the growing vascular structure as a quality control before implantation (maximally achieved ultrasound resolution 65 μm at 15 MHz). To withstand the harsh conditions of steam sterilization (120°C for 20 min), all electronics were encapsulated. With such a comprehensive physiologically conditioning, sensing, and imaging bioreactor system, all the requirements for a successful cultivation of vascular grafts are available now.

Acellular Small-Diameter Tissue-Engineered Vascular Grafts

“…One group consists of self-assembled TEVGs, and the second of scaffold-based TEVGs [6]. Scaffold-based TEVGs include three key elements [7]: the scaffold, the seed cell, and the bioreactor [8,9]. The scaffold can be prepared using natural polymers, synthetic polymers, hybrid polymers, or a decellularized matrix.…”

Current Progress in Vascular Engineering and Its Clinical Applications

“…Following these findings, Niklason and colleagues pioneered the development of bioreactors as in vitro biomimetic flow systems [159]. By emulating the physiological conditions that blood vessels experience in vivo, other groups also demonstrated that the TEVGs matured to mimic the properties of native vessels through increased ECM formation, VSMC and EC differentiation, as well as migration [160,161]. Advancements in bioreactor technology have also minimised the risk of contamination through the automation of tissue culture, wireless data transfer and pH monitoring.…”

“…Advancements in bioreactor technology have also minimised the risk of contamination through the automation of tissue culture, wireless data transfer and pH monitoring. However, the complexity of conditions required to produce grafts that fit these purposes remains a challenge [160,162].…”

Vascular implants – new aspects for in situ tissue engineering

“…Another comprehensive cultivation process for TEVGs (featuring, e.g., automated concentration measurement of glucose or lactate, online 3D visualization, shear stress analysis, etc.) has been elaborated and improved over several years at the Leibniz University of Hannover in [ 22 , 23 , 24 ]. This rotational‐perfusion bioreactor system comprises an automated monitoring and control of physiological conditions, and an online 3D visualization and geometrical analysis system.…”