title: A new approach to heart valve tissue engineering: mimicking the heart ventricle with a ventricular assist device in a novel bioreactor.
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% CO(2) 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.
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, Bioengineering Division, São Paulo, Brazil.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaasi
authors.forename: Idágene A
authors.initials: IA
authors.lastname: Cestari
authors.forename: Noedir A G
authors.initials: NA
authors.lastname: Stolf
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Leirner
authors.forename: Ole
authors.initials: O
authors.lastname: Hassager
authors.forename: Ismar N
authors.initials: IN
authors.lastname: Cestari
mesh_terms: D000818:Animals; D019149:Bioreactors; D003187:Compliance; D006351:Heart Valves / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D006352:Heart Ventricles / Q000033:anatomy & histology*; D006353:Heart-Assist Devices; D011312:Pressure; D051381:Rats; D012212:Rheology; D013242:Sterilization; D034421:Sus scrofa; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*