A New Bioreactor for the Development of Tissue-Engineered Heart Valves

Abstract

This paper reports the design, manufacturing, and characterization of a new bioreactor dedicated to the development of tissue-engineered heart valve substitutes. First, a comprehensive review of the state of the art in bioreactors is presented and a rigorous classification is put forward. The existing bioreactors found in literature are organized in three groups and discussed with respect to their quality of reproduction compared to the physiological environment. The bioreactor architecture is then decomposed into basic components which may be grouped together in different arrangements, and the well-known Windkessel approach is used to study the global behavior of the system. Then, the new design, which is based on a synthesis of the features of the most evolved systems as well as on new improvements, is explained in detail. Optimal fluid dynamics are obtained with the presented bioreactor through carefully designed components and an advanced computer-controlled actuator. This allows a very accurate reproduction of physiological parameters, namely the pulsating flow rate and pressure. Finally, experimental results of flow rate and pressure waveforms are presented, where an excellent correlation with physiological measurements can be observed.

Progress in developing a living human tissue-engineered tri-leaflet heart valve assembled from tissue produced by the self-assembly approach

“…Further studies will be necessary to assess the functionality of those engineered valves in a bioreactor simulating aortic blood flow conditions [74]. There are still important challenges to overcome in order to prove functionality and efficiency of this new valve model.…”

Cells, scaffolds and bioreactors for tissue-engineered heart valves: a journey from basic concepts to contemporary developmental innovations☆

“…To achieve such regimes, peristaltic, centrifugal, or pneumatic pumps have been commonly used, coupled with programmable waveform generators that recreate the cardiac physiological flow. Moreover, particular attention should be addressed to the simulation of the in vivo elastic properties of vessels: this is usually gained implementing the machinery with a compliance chamber designed for the simulation of the elastic loading sustained in vivo by the arteries, responsible for the delay and the shape of the pressure waveform [54]. Flow resistors are also of some importance to reproduce the vasculature narrowing in precapillary arterioles, capillaries, and veins as well; they are usually positioned downstream of the TEHV.…”

A Bioreactor with Compliance Monitoring for Heart Valve Grafts

“…Indeed, it is now commonly accepted that the in vitro growth of engineered tissues, which are meant to play a mechanical role once implanted in vivo, must be accompanied by adequate mechanical stimuli in order to improve the relevant mechanical properties of the construct, such as the mechanical strength and stiffness. 1,15,20,22 Mechanical stimulation plays a key role in enhancing cell adhesion and proliferation as well as in stimulating the biosynthesis of the extracellular matrix (ECM) components and their structural architecture. Mechanical stimulation in dynamic bioreactors for VC growth usually relied on shear stress stimulation, 13 strain stimulation, 19,24 or a combination of the two; 8,10,14,21,23 cyclic flexural stimulation was also experimented.…”