Injectable materials for the treatment of myocardial infarction and heart failure: the promise of decellularized matrices

Abstract

Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-based delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair.

Fig. 1

Decellularized ventricular ECM and non-decellularized porcine ventricular tissue (hematoxylin and eosin-stained sections). a, b Intact decellularized ventricular ECM prior to processing. c Intact non-decellularized ventricular tissue. Scale bars, 100 μm. Note the absence of cells in the decellularized ECM. Reprinted with permission from [80]

Fig. 2

Decellularized and non-decellularized human and porcine pericardial tissue (hematoxylin and eosin-stained sections). a, b Human; c, d Porcine; a, c Non-decellularized pericardial tissue; b, d Decellularized pericardial ECM. Scale bars, 500 μm. Note the absence of cells in the decellularized ECM. Reprinted with permission from [81]

Fig. 3

Decellularization process of ventricular extracellular matrix. a Decellularized, lyophilized (dried) ECM. b Milled powder. c Solubilized myocardial matrix in a 1-mL syringe, prepared for injection

Fig. 4

In vivo gelation of injectable myocardial and pericardial matrix scaffolds (hematoxylin and eosin-stained sections). a Arrow indicates area of injected myocardial matrix, and the inset is intact decellularized ventricular ECM prior to processing. Scale bar, 100 μm. Note the similar structure of the self-assembled matrix to the decellularized ECM. b Arrow indicates area of injected human pericardial matrix. Scale bar, 500 μm. c Arrow indicates area of injected porcine pericardial matrix. Scale bar, 500 μm. Reprinted with permission from [80, 81]