Modeling the Role of Oscillator Flow and Dynamic Mechanical Conditioning on Dense Connective Tissue Formation in Mesenchymal Stem Cell–Derived Heart Valve Tissue Engineering

Living tissue–engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. Although a myriad of external stimuli are available in current bioreactors (e.g., oscillatory flows and mechanical conditioning), there remain significant bioengineering challenges in determining and quantifying parameters that lead to optimal extracellular matrix (ECM) development for the long-term goal of engineering TEHVs exhibiting tissue architecture and functionality equivalent to native tissue. It has become axiomatic that in vitro mechanical conditioning promotes engineered tissue formation, either in organ-level bioreactors or in tissue-level bioreactors with idealized-geometry tissue engineering (TE) constructs [2–5]. However, the underlying mechanisms remain largely unknown. Efforts to date have been largely empirical, but a two-pronged approach involving novel theoretical developments and close-looped designed experiments is necessary to reach a better mechanistic understanding of the...