Design and hydrodynamic evaluation of a novel pulsatile bioreactor for biologically active heart valves

• Published in: Annals of biomedical engineering Vol. 32; no. 8; pp. 1039 - 1049
• Main Authors: Hildebrand, Daniel K, Wu, Zhongjun J, Mayer, Jr, John E, Sacks, Michael S
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.08.2004
• Subjects: Bacteria; Bioprosthesis; Bioreactors; Equipment Design; Equipment Failure Analysis - instrumentation; Heart Valve Prosthesis; Hemorheology - instrumentation; Hemorheology - methods; Humans; Microfluidics - instrumentation; Microfluidics - methods; Proteins; Pulsatile Flow; Tissue Culture Techniques - instrumentation; Tissue Culture Techniques - methods; Tissue Engineering - instrumentation; Tissue Engineering - methods
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1114/B:ABME.0000036640.11387.4b

Biologically active heart valves (tissue engineered and recellularized tissue-derived heart valves) have the potential to offer enhanced function when compared to current replacement value therapies since they can possibly remodel, and grow to meet the needs of the patient, and not require chronic medication. However, this technology is still in its infancy and many fundamental questions remain as to how these valves will function in vivo. It has been shown that exposing biologically active tissue constructs to pulsatile pressures and flows during in vitro culture produces enhanced extracellular matrix protein expression and cellularity, although the ideal hydrodynamic conditioning regime is as yet unknown. Moreover, in vitro organ-level studies of living heart valves aimed at studying the remodeling processes require environments that can accurately reproduce in vivo hemodynamics under sterile conditions. To this end, we have developed a system to study the effects of subjecting biologically active heart valves to highly controlled pulsatile pressure and flow waveforms under sterile conditions. The device fits inside a standard incubator and utilizes a computer-controlled closed loop feedback system to provide a high degree of control. The mean pressure, mean flow rate, driving frequency, and shape of the pulsatile pressure waveform can be changed automatically in order to simulate both physiologic and nonphysiologic hemodynamic conditions. Extensive testing and evaluation demonstrated the device's ability to subject a biologically active heart valve to highly controlled pulsatile waveforms that can be modulated during the course of sterile incubation.