Development of a Novel Bioreactor for the Mechanical Loading of Tissue-Engineered Heart Muscle

Abstract

In this study, we describe a novel bioreactor system to deliver controlled stretch protocols to bioengineered heart muscle (BEHM) constructs. Our primary objective was to evaluate the effect of mechanical stretch on the contractile properties of three-dimensional cardiac constructs in vitro. BEHMs were formed by culturing primary neonatal cardiac myocytes in a fibrin gel using a method previously developed in our laboratory. A custom bioreactor system was designed using SolidWorks (Concord, MA) and structural components were manufactured using fusion deposition modeling. We utilized the bioreactor to evaluate the effect of 2-, 6-, and 24-hour stretch protocols on the stretch-induced changes in contractile function of BEHMs. We were able to demonstrate compatibility of the bioreactor system with BEHMs and were able to stretch all the constructs with zero incidence of failure. We found that loading the constructs for 2, 6, and 24 hours during a 24-hour period using a stretch protocol of 1 Hz, 10% stretch did not result in any significant change in the active force, specific force, pacing characteristics, and morphological features. In this study, we demonstrate compatibility of a novel bioreactor system with BEHMs and the stability of the BEHMs in response to stretch protocols.