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A new approach to heart valve tissue engineering: mimicking the heart ventricle with a ventricular assist device in a novel bioreactor
Authors:Andreas Kaasi  Idágene A. Cestari  Noedir A. G. Stolf  Adolfo A. Leirner  Ole Hassager  Ismar N. Cestari
Affiliation:1. Heart Institute (InCor), University of S?o Paulo Medical School, Bioengineering Division, S?o Paulo, Brazil;2. M.Sc. (Eng) Program, Medicine and Technology, Technical University of Denmark and University of Copenhagen, Denmark;3. Danish Polymer Centre, Department of Chemical and Biochemical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark;4. Heart Institute (InCor), University of S?o Paulo Medical School, Department of Thoracic and Cardiovascular Surgery, S?o Paulo, Brazil
Abstract:The ‘biomimetic’ approach to tissue engineering usually involves the use of a bioreactor mimicking physiological parameters whilst supplying nutrients to the developing tissue. Here we present a new heart valve bioreactor, having as its centrepiece a ventricular assist device (VAD), which exposes the cell–scaffold constructs to a wider array of mechanical forces. The pump of the VAD has two chambers: a blood and a pneumatic chamber, separated by an elastic membrane. Pulsatile air‐pressure is generated by a piston‐type actuator and delivered to the pneumatic chamber, ejecting the fluid in the blood chamber. Subsequently, applied vacuum to the pneumatic chamber causes the blood chamber to fill. A mechanical heart valve was placed in the VAD's inflow position. The tissue engineered (TE) valve was placed in the outflow position. The VAD was coupled in series with a Windkessel compliance chamber, variable throttle and reservoir, connected by silicone tubings. The reservoir sat on an elevated platform, allowing adjustment of ventricular preload between 0 and 11 mmHg. To allow for sterile gaseous exchange between the circuit interior and exterior, a 0.2 µm filter was placed at the reservoir. Pressure and flow were registered downstream of the TE valve. The circuit was filled with culture medium and fitted in a standard 5% CO2 incubator set at 37 °C. Pressure and flow waveforms were similar to those obtained under physiological conditions for the pulmonary circulation. The ‘cardiomimetic’ approach presented here represents a new perspective to conventional biomimetic approaches in TE, with potential advantages. Copyright © 2010 John Wiley & Sons, Ltd.
Keywords:tissue engineering  heart valves  bioreactor  ventricular assist device  Windkessel  cardiomimetic approach
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