Establishing the Framework for Fabrication of a Bioartificial Heart

Abstract

There is a chronic shortage of donor hearts. The ability to fabricate complete bioartificial hearts (BAHs) may be an alternative solution. The current study describes a method to support the fabrication and culture of BAHs. Rat hearts were isolated and subjected to a detergent based decellularization protocol to remove all cellular components, leaving behind an intact extracellular matrix. Primary cardiac cells were isolated from neonatal rat hearts, and direct cell transplantation was used to populate the acellular scaffolds. Bioartificial hearts were maintained in a custom fabrication gravity fed perfusion culture system to support media delivery. The functional performance of BAHs was assessed based on left ventricle pressure and on electrocardiogram. Furthermore, BAHs were sectioned and stained for the whole heart cardiac tissue distribution and for cardiac molecules, such as α-actinin, cardiac troponin I, collagen type I, connexin 43, von Willebrand factor, and ki67. Bioartificial hearts replicated a partial subset of properties of natural rat hearts. The current study provided a method for fabrication of a BAH and revealed challenges toward BAH fabrication with functional performance metrics of natural mammalian hearts.

Electrophysiological Stimulation of Whole Heart Constructs in an 8‐Pole Electrical Field

“…This illuminates a clear shifting up of the beating rates by the impact of stimulation that further shows to be significant for the mean value. In direct comparison to a current injection principle that is also based on utilizing neonatal rat cardiomyocytes in decellularized whole rat hearts, our 8‐pole field stimulation concept could roughly double the mean voltage amplitude and increase the beating rate by 20%, although this seems to rather adapt to the stimulation frequency of 3 Hz . Interestingly, the same effect has been reported for beating rates of electrically stimulated fibrin‐based constructs .…”

“…By their pioneering work, Ott and colleagues have shown the fundamental cornerstones presented by a bioreactor system to provide perfusion‐culture of the WHC and a biophysical stimulation concept providing organ‐typical physiological effects . For biophysical simulation of WHC, the application of current injection by directly inserted or contacted electrodes has shown promising results . In addition to this, the impact of whole left ventricular stretching as another key‐stimulus for maturation of WHC has been shown recently .…”

3D bioprinting and its potential impact on cardiac failure treatment: An industry perspective

“…2). The field of cardiac tissue engineering as a whole is targeted to bioengineering 3D heart muscle or cardiac patches, [12][13][14][15][16] biological pumps, 17 ventricles, 18 valves, 19 blood vessels, 20 and entire bioartificial hearts, 21 with tremendous progress being made on all fronts. Cardiac patches or 3D heart muscle are planar tissue constructs that replicate the anatomical and functional characteristics of mammalian heart muscle tissue.…”

“…There have been many publications describing the fabrication of a total bioartificial heart, almost all of which relied upon acellular scaffolds populated with either neonatal ventricular rat myocytes (NVRMs) or induced pluripotent stem (iPS) derived cardiomyocytes 21,[25][26][27][28][29][30] (Table I). In almost all cases, functional performance has been demonstrated by measuring left ventricular pressure and found to be 1 mm Hg.…”

Current State of the Art in Ventricle Tissue Engineering

“…There is a large body of literature describing methods to bioengineer cardiovascular tissue constructs (13)(14)(15)(16)(17), based on which a methodological process has now evolved ( Figure 2). The first step in the process is cell sourcing, generating a large number of contractile cardiomyocytes (CMs).…”