UC San Diego

Over the past several decades, coronary heart disease leading to myocardial infarction (MI) and subsequent heart failure (HF) has continued to the leading cause of death in the Western world and worldwide. Sudden death and limited renewal of cardiomyocytes post-myocardial leads to progressive expansion of tissue necrosis, negative left ventricular remodeling, and loss of function eventually causing heart failure. Treatments for end-stage HF, heart transplants and left ventricular assist devices, are hampered by healthy organ availability, limited medical resources, and negative impacts on patients’ quality of life, thus prompting the need for novel therapies. Amongst hydrogel therapies, Injectable extracellular matrix (ECM) hydrogels derived from decellularized porcine left ventricular tissue have rapidly developed into

a leading injectable hydrogel therapy based on shown therapeutic potential post-myocardial infarction demonstrated in both small and large animal models. To continue developing this and general decellularized platforms, improved understanding of the underlying cellular mechanisms contributing to the observed myocardial repair is needed. Based on previous transcriptomic and histological assessments, further examination into the cellular response of cardiomyocyte and immune cell populations is studied to determine their involvement in the observed tissue repair. We show with pre-labeling methods to track events of DNA synthesis and proliferation in in vivo and in vitro models, respectively, that myocardial matrix material properties relevant to supporting proliferative characteristics in cardiomyocytes. Additional examination of immune cell populations has determined that the myocardial matrix supports a dynamic pro-inflammatory to pro-remodeling immune response indicative of induced tissue repair. Finally, we determined the involvement of mast cells in the biomaterial induced tissue repair, highlighting this understudied cell type for the field to consider when developing new biomaterial therapies.