Abstract
Purpose Nearly 22 million people suffer from heart failure (HF) worldwide. Heart transplantation is the only viable treatment for HF, but donor organ shortage fails to meet clinical demand. A bioartificial heart could overcome this limitation. The first step towards development is the generation of a perfusable cardiac matrix. Herein, we introduce a standard protocol for decellularizing human hearts and characterize the resulting scaffolds. Methods and Materials Ten human hearts unsuitable for transplantation were retrieved for research, 4 of which were donation after cardiac death (DCD) donors. Applying antegrade coronary perfusion, hearts were decellularized using sodium dodecyl sulfate and subsequent washes. Valve competency and coronary angiographies were performed with a pressure-controlled pump in a fluoroscopy suite. ECM characterization was done by immunohistochemistry (IHC) for matrix proteins and cardiac cell markers, scanning electron microscopy (SEM), and equibiaxial mechanical testing. Results Human hearts can be decellularized using antegrade coronary perfusion. IHC and SEM analysis revealed a lack of cells, negative staining for cardiac markers, and intact basement membranes. Valve competency showed all four heart valves exhibited higher regurgitant flow during physiological pressures, though decelled mitral valves showed statistically higher flow. Coronary angiography confirmed preservation of patent coronaries. IHC analysis showed decelled human hearts maintain ECM protein content and structure. Equibiaxial testing of decelled myocardium exhibited non-linear behavior and similar elastic modulus along both axes. Hearts from DCD donors were successfully decellularized, with similar outcomes to non-DCD hearts. Conclusions Decellularization of human hearts renders a native cardiac matrix with ECM-protein retention and perfusable coronary conduits. Successful decellularization of DCD hearts may provide a significant source of new donor grafts, from organs previously considered unsuitable for transplant.
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